Thank you for the clarification. I will conduct research on strategies to minimize colorectal cancer recurrence, including general recommendations and those specifically tailored to your mutations.

The research will cover six categories:

n1. Exercise/activity recommendations n2. Dietary considerations (foods, beverages, and spices) n3. OTC medications n4. Off-label prescription medications n5. Prescription medications n6. Potential animal drugs worth studying further

Each tactic will be graded on a 1-5 scale for research quality, side effects, and effectiveness, as per your request. I will ensure to clearly distinguish between general colorectal cancer guidance and mutation-specific insights. I will update you once the research is ready.

Minimizing Colorectal Cancer Recurrence: A Comprehensive Review

Exercise and Physical Activity

Regular physical activity is one of the most strongly recommended lifestyle changes for colorectal cancer survivors. Guidelines generally advise at least 150 minutes of moderate-intensity or 75 minutes of vigorous aerobic exercise per week, with 300 minutes per week as an optimal target

www.cancer.org. This includes activities like brisk walking, jogging, cycling, or swimming. In addition, incorporating strength training twice per week is encouraged to rebuild muscle and improve overall fitness (e.g. weightlifting or resistance band exercises)pmc.ncbi.nlm.nih.gov. Such exercise not only improves quality of life and reduces treatment-related fatiguepmc.ncbi.nlm.nih.gov, but is also linked to lower recurrence and better survival after colon cancer. Observational studies consistently show that survivors who stay active have a significantly lower risk of recurrence and cancer-related death than those who are sedentarypmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov. For example, stage III colon cancer patients who engaged in physical activity at least a few times per month had about a 18% improvement in disease-free survival (hazard ratio ~0.82) compared to those exercising less than once a monthpmc.ncbi.nlm.nih.gov. Some data even suggest a dose-response effect – in one trial, 300 minutes/week of exercise was associated with reduced biomarkers of recurrence risk and better outcomes than 150 minutespmc.ncbi.nlm.nih.gov.

Mutation-Specific Insights: The benefits of exercise appear to apply broadly to colorectal cancer survivors, regardless of common tumor mutations. In one analysis, higher physical activity was associated with improved outcomes whether or not tumors had mutations in KRAS, BRAF, or other markers

pmc.ncbi.nlm.nih.gov. Interestingly, sedentary lifestyle and obesity have been linked to a greater incidence of colorectal tumors harboring KRAS mutationspmc.ncbi.nlm.nih.gov, implying that exercise and weight control may be particularly relevant for patients with KRAS-driven cancers. However, no specific type of exercise is uniquely required for KRAS G12C or other mutations – the standard recommendations (aerobic + resistance training) are believed to confer benefit across all genetic subtypes.

Research Quality: 4/5. Numerous large human studies and meta-analyses support exercise for reducing colorectal cancer mortality and recurrence risk

pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov. While these are mostly observational (not randomized), the evidence is consistent and strong. Ongoing randomized trials (e.g. the CHALLENGE trial) are expected to provide level-5 evidence, but current data in thousands of survivors already make exercise one of the best-supported lifestyle interventions.
Side Effects: 1/5. Physical activity is generally very safe. Unlike drugs, exercise has no direct toxic side effects. The main risks are minor, such as muscle soreness or occasional injuries if one overexerts or has preexisting joint issues. Overall, the health benefits (cardiovascular fitness, mood improvement, etc.) far outweigh these risks for most people. (Patients should of course tailor activity to their fitness level and heal from surgery before vigorous exercise.)
Effectiveness: 4/5. Exercise provides a meaningful reduction in recurrence risk and improvement in survival. Studies have found about a 30–50% lower risk of cancer recurrence or death in the most active survivors versus the least activepmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov. This magnitude is comparable to some medical interventions. While exercise is not a guaranteed prevention, it exerts beneficial effects on insulin levels, inflammation, and immune function that meaningfully improve odds of staying cancer-free.

Dietary Considerations

Diet plays a pivotal role in cancer survivorship. General recommendations for colorectal cancer survivors mirror those for cancer prevention: emphasize a plant-focused, high-fiber diet rich in vegetables, fruits, whole grains, and legumes, while limiting processed and red meats, saturated fats, and refined sugars

www.dana-farber.org www.dana-farber.org. A large study of stage III colon cancer patients found that those who most closely followed a “Western” diet (high in red meat, processed foods, sweets, and refined grains) had a 3.5-fold higher risk of recurrence than those eating the least Western-like dietwww.dana-farber.org www.dana-farber.org. Conversely, patients whose eating patterns were closer to a “prudent” diet (high in vegetables, fruits, poultry, and fish) had significantly better survivalwww.dana-farber.org www.dana-farber.org. The protective effect of a healthy diet persisted even after accounting for factors like age, stage, and activity level. Key dietary elements to consider include:

Fiber and Whole Foods: Diets high in dietary fiber (from whole grains, beans, veggies, etc.) are associated with improved colorectal cancer outcomes. Fiber may bind carcinogens and improve gut health. While some randomized trials of fiber supplementation alone did not dramatically cut polyp recurrence, observational evidence suggests higher whole-food fiber intake reduces colorectal cancer mortality and recurrence (quality evidence from large cohorts). There are virtually no adverse side effects to eating natural high-fiber foods aside from minor gastrointestinal gas, so this is universally encouraged. Research Quality: 4/5 (strong observational data and biological plausibility), Side Effects: 1/5, Effectiveness: 3/5 (moderate risk reduction). Maintaining a healthy body weight through diet is also important, as obesity raises recurrence risk

pmc.ncbi.nlm.nih.gov.
Limit Red and Processed Meat: Red and processed meats are high in heme iron and nitrates, which can promote carcinogens in the gut. In survivors, high consumption of these foods correlates with worse outcomes

www.dana-farber.org. Reducing red meat to moderate levels (or replacing it with poultry/fish) and avoiding processed meats (bacon, sausage, deli meats) can help. Research Quality: 4/5 – the link between processed meat and colorectal cancer is well-established in epidemiology, including survivorship cohortswww.dana-farber.org. Side Effects: 1/5 – the “risk” of eating less bacon is essentially none (aside from dietary preference). Effectiveness: 4/5 – adopting a diet with minimal processed/red meat is likely to meaningfully lower recurrence risk, given the large hazard increase seen with a Western dietwww.dana-farber.org.
Fish and Omega-3 Fats: Eating fish (especially fatty fish rich in omega-3 fatty acids like salmon, tuna, sardines) appears beneficial. A study of 1,011 stage III colon cancer patients reported that those who ate dark-meat fish ≥2 times per month had significantly longer recurrence-free survival – about a 39% lower hazard of recurrence (HR ~0.61) compared to those who ate no fish

www.cancernetwork.com. Higher intake of marine omega-3 polyunsaturated fats was linked to improved disease-free survival, particularly in tumors expressing COX-2www.cancernetwork.com. Omega-3s have anti-inflammatory effects that may inhibit tumor growth. For those who don’t eat fish, a fish oil supplement (discussed below in OTC supplements) is an alternative. Research Quality: 4/5 (prospective human data suggests benefit), Side Effects: 1/5 (fish or fish oil in moderate amounts is safe; watch for mercury in excessive fish consumption), Effectiveness: 3/5 (likely a moderate protective effect on recurrence). Notably, this effect is general, not tied to a specific mutation – though patients with COX-2 overactive tumors (often associated with APC mutations and inflammation) might benefit most from the anti-inflammatory omega-3s.
Antioxidant-Rich Foods and Spices: Many plant-based foods contain bioactive compounds that may have anti-cancer properties. For example, cruciferous vegetables (broccoli, cauliflower, kale) contain sulforaphane which has shown tumor-inhibiting effects in lab studies. Allium vegetables (garlic, onions) have organosulfur compounds that may help reduce carcinogen formation. Turmeric (curcumin) is a spice with potent anti-inflammatory and anti-tumor activity in preclinical models. In familial polyposis patients (who often have APC mutations), curcumin combined with quercetin reduced polyp number in a small trial

www.cancer.gov, and curcumin is being investigated for preventing recurrence (phase II trials show it can favorably affect inflammatory markers in the colonwww.cancer.gov). Green tea contains catechins (like EGCG) that have been linked to cancer prevention; indeed, a 3-year randomized trial of green tea extract suggested a reduction in new colon adenomas (precancerous polyps) in high-risk individualspubmed.ncbi.nlm.nih.gov, though more research is needed for definitive proof. Overall, diets rich in colorful fruits, vegetables, herbs, and spices can provide these micronutrients. While no single “superfood” is proven to prevent recurrence, a broad intake likely creates a synergistic protective effect. These dietary compounds are very safe at culinary doses. Research Quality: 2/5 (evidence mostly from cell/animal studies and small human trials), Side Effects: 1/5 (no significant side effects from consuming these foods; supplements like concentrated curcumin can cause mild GI upset in some), Effectiveness: 2/5 (potential small additive effect in reducing recurrence risk, but not a substitute for proven therapies). They should be viewed as supportive measures. Notably, these strategies are generally applicable to all survivors; there are no specific dietary modifications proven exclusively beneficial for KRAS, APC, PIK3CA, or other mutations, aside from the overall anti-inflammatory diet which may particularly help those with pro-inflammatory tumor pathways (e.g. APC mutation often leads to COX-2 upregulation, which a plant-rich diet might counter).
Alcohol and Sugar: It’s advisable to limit alcohol consumption, as alcohol is a known risk factor for colorectal cancer. Survivors who drink heavily could increase their chance of a new primary tumor. The World Cancer Research Fund recommends no more than 1 drink per day for women or 2 for men – and ideally abstaining

www.cancer.org www.cancer.org. Similarly, a diet high in refined sugars (sweets, sugary drinks) can contribute to obesity and insulin spikes, which may feed tumor growth. Limiting sugary foods and beverages is prudent. Research Quality: 3/5 (epidemiological links between high sugar intake and worse cancer outcomes are suggestive), Side Effects: 1/5 (reducing excess sugar has health benefits), Effectiveness: 2/5 (moderate reduction in risk via weight control and metabolic health).

In summary, a Mediterranean-style or plant-based diet aligning with these principles is recommended for all colorectal cancer survivors. It addresses multiple pathways (insulin, inflammation, microbiome health) and can work synergistically with other measures.

Research Quality (Overall Diet): 4/5. There is large-scale human evidence linking diet to recurrence outcomes. The cornerstone study by Meyerhardt et al. in 1,000+ patients (JAMA 2007) provides level-4 evidence that diet quality influences recurrence

www.dana-farber.org. Additionally, multiple cohort studies and even some randomized polyp prevention trials inform these recommendations. While randomized dietary interventions for recurrence are challenging, the consistency of observational data yields high confidence.
Side Effects (Dietary Changes): 1/5. Adopting a healthier diet is virtually risk-free. Unlike medications, eating more vegetables or cutting back on processed meat does not cause harmful side effects – on the contrary, it improves overall health (cardiovascular, etc.). The main “downsides” might be adjusting shopping and cooking habits or potential mild digestive changes (e.g. increased fiber causing bloating initially), but these are manageable.
Effectiveness: 4/5. Diet can have a meaningful impact on recurrence risk, especially when changes are substantial (e.g. eliminating a heavily Western diet). As noted, a poor diet can triple the risk of recurrencewww.dana-farber.org, so switching to a prudent diet can significantly improve odds. While diet alone is not a magic bullet, it forms an important part of an overall strategy – likely contributing on the order of tens of percentage points of risk reduction when optimally followed, and it also helps other conditions (weight, heart health) that keep a survivor fit for any additional treatments.

Over-the-Counter (OTC) Medications and Supplements

Certain non-prescription medications and supplements have shown promise in reducing colorectal cancer recurrence or risk. It’s important to evaluate the strength of evidence and potential risks for each:

Aspirin (Low-Dose Aspirin, e.g. 81 mg daily): This is one of the most studied agents for colorectal cancer prevention. Aspirin is an NSAID that blocks COX-1/COX-2 enzymes, reducing inflammation and prostaglandin-driven tumor growth. Epidemiological studies first noted that colon cancer patients who took regular aspirin had better survival. More recently, a randomized controlled trial (ALASCCA trial) provided direct evidence: among patients with PIK3CA-mutated colorectal cancer, 3 years of daily aspirin cut recurrence risk by about 50% compared to placebo

www.oncnursingnews.com www.oncnursingnews.com. The hazard ratio for recurrence in aspirin users was ~0.49 in that subgroupwww.oncnursingnews.com. This is a major finding indicating aspirin is highly effective for tumors with PIK3CA mutations. (Mechanistically, PIK3CA mutations activate the PI3K pathway, which may make tumors more dependent on inflammatory signaling – thus more sensitive to aspirin’s effectswww.oncnursingnews.com.) Interestingly, the trial also suggested that other mutations in the PI3K/PTEN pathway might predict benefit, potentially expanding aspirin’s utility to over one-third of non-metastatic CRC patientswww.oncnursingnews.com. Even outside of PIK3CA mutants, aspirin likely has some preventive effect: for example, in Lynch syndrome (hereditary MSI-high cancers), 600 mg aspirin for 2+ years halved colorectal cancer incidence after a decade of follow-up (level-5 evidence from the CAPP2 trial). Guidelines are moving toward recommending low-dose aspirin for some survivors, especially if cardiovascular risk factors make aspirin potentially doubly beneficial.

Research Quality: 5/5. The evidence for aspirin is robust – including large-scale observational studies and placebo-controlled trials

www.oncnursingnews.com www.oncnursingnews.com. Aspirin’s preventive role in colorectal neoplasia is well established (it’s even FDA-approved for reducing hereditary polyp burden in FAP at high doses, and recommended by USPSTF for certain adults to prevent colon cancer). The recent ALASCCA RCT specifically in survivors elevates this to the highest evidence level.
Side Effects: 3/5. Aspirin is generally well tolerated at low dose, but it is not free of risk. The main concern is gastrointestinal bleeding – aspirin can irritate the stomach lining and impair blood clotting, leading to ulcers or bleeds. Most side effects are mild (heartburn, minor bruising), but serious bleeding (GI bleed or hemorrhagic stroke) can occur in a small fraction of users, especially at higher doses or in those with risk factors. The risk of fatal complications is low (likely well under 1%), but because any preventative use is long-term, this must be weighed. Overall, we rate side effects 3/5: not negligible, but moderate. Patients should consult their doctor; often the benefits outweigh risks in those with higher recurrence risk (particularly PIK3CA-mutant patientswww.oncnursingnews.com) or concomitant cardiovascular disease.
Effectiveness: 5/5. For the right patient, aspirin offers a meaningful reduction in recurrence risk. In PIK3CA-mutated cases, a ~50% risk reduction is dramaticwww.oncnursingnews.com. Even in unselected patients, meta-analyses have found that post-diagnosis aspirin use is associated with improved survival. Thus, aspirin can be considered one of the most effective chemopreventive agents available. It’s important to note the effectiveness may be lower in aspirin-resistant tumors (e.g. those without the PI3K pathway alterations), perhaps on the order of a more modest ~10-15% improvement in recurrence-free survival observed in some cohorts. But given its low cost and dual benefits (cancer and heart disease prevention), aspirin is often recommended after discussing individual risk factors.
Vitamin D: Vitamin D, obtained from sunlight or supplements (typically vitamin D3), has emerged as a potential cancer preventative. Colorectal cancer patients with higher blood levels of 25(OH)D tend to have better survival and lower recurrence rates

www.dana-farber.org. Vitamin D may enhance immune surveillance and promote differentiation in colon cells. A notable trial in Japan (AMATERASU trial) tested 2,000 IU/day of vitamin D3 vs placebo in patients with resected stage I-III colorectal cancer. It found a non-significant trend toward improved relapse-free survival overall, but a significant benefit in a subgroup of patients with wild-type p53 tumors (suggesting those patients saw reduced relapse with vitamin D)jamanetwork.com. Another trial in metastatic CRC (SUNSHINE trial) showed that adding high-dose vitamin D to chemotherapy improved progression-free survival by a few monthswww.dana-farber.org. While definitive proof in the adjuvant setting is pending (a large UK-US trial called “#D-Health” or similar is underway), many oncologists check vitamin D levels and recommend supplementation into the optimal range (>30 ng/mL) because of its low risk.

Research Quality: 4/5. There is strong associative evidence (prospective studies) linking vitamin D with outcomes

www.dana-farber.org. Randomized trial evidence is mixed – one trial did not show a statistically significant benefit overalljamanetwork.com, though design and power may be factors. The body of evidence is still evolving; hence we give it 4 (not fully conclusive RCT at level 5 yet, but very suggestive human data).
Side Effects: 1/5. Vitamin D at moderate doses (1000–2000 IU daily) is very safe. Side effects are negligible unless one takes an extreme overdose, which could cause high calcium levels. When taken as recommended, it does not cause noticeable side effects. (It’s cheap and over-the-counter, too.)
Effectiveness: 3/5. Likely moderate effect. Sufficient vitamin D might reduce recurrence risk by perhaps ~15-20% (hypothesized from observational risk differences), though exact figures await further trials. It’s certainly beneficial for overall health (bone strength, immune function), and might modestly improve cancer outcomes – enough to justify correcting deficiency. We consider it moderately effective as part of a broader regimen, even if not a standalone powerful intervention.
Calcium: Calcium supplementation has been tested for colorectal neoplasia prevention, based on observations that calcium binds bile acids and fatty acids in the gut and may protect the colon lining. In randomized trials among people with a history of polyps, calcium (1200-2000 mg/day) produced a modest reduction in the formation of new adenomatous polyps

pmc.ncbi.nlm.nih.gov. This suggests a potential to prevent progression to cancer. However, calcium alone has not been shown to significantly change cancer recurrence in those already treated for cancer – its effect seems more on precursor lesions. Still, many survivors ensure adequate calcium intake (from diet or supplements) for general health, and it could have a minor preventative benefit.

Research Quality: 3/5. Evidence comes from human trials in polyp prevention (level 4), but not specifically large trials in cancer survivors. The data are somewhat mixed on effectiveness (some polyp trials positive, others neutral).
Side Effects: 1/5. Calcium at recommended doses is safe for most people. High doses could cause kidney stones in susceptible individuals, or constipation, but serious effects are rare.
Effectiveness: 2/5. Slight effect at best for cancer recurrence. While calcium may reduce polyp formation by ~15-20%, translating that to actual cancer prevention is uncertain. It’s likely not a game-changer for someone who has already had cancer, but it’s a low-risk adjunct that might contribute a little to risk reduction (and supports bone health, which is important especially if treatments induced any bone loss).
Multivitamins and Others: Many survivors consider general multivitamins or specific supplements (vitamin C, E, B vitamins, etc.). So far, no high-quality evidence shows that taking high doses of any antioxidant vitamins will reduce recurrence – in fact, a large trial of multivitamin use in stage III colon cancer did not find any improvement in outcomes compared to placebo. Thus, routine supplementation beyond ensuring no deficiencies is not strongly supported. One exception might be folate: adequate folate (vitamin B9) from diet is associated with lower colorectal cancer risk, but high-dose folic acid supplements after cancer diagnosis have not shown benefit and might even promote growth of residual tumor cells if given in excess. Therefore, it’s recommended to get folate from a balanced diet (leafy greens, legumes) rather than high-dose pills post-cancer. Probiotics and maintaining a healthy gut microbiome are an emerging area of interest (since gut bacteria can influence inflammation and metabolize fiber into protective compounds like butyrate), but specific probiotic supplements have not been proven to reduce recurrence – though they may help with digestion or after antibiotic use. In summary, a general multivitamin is fine to cover nutritional gaps, but evidence level is low (1-2/5) for any impact on recurrence, and thus no specific OTC vitamin (apart from D and calcium as discussed) can be firmly recommended for recurrence prevention. Always discuss supplements with a healthcare provider to avoid interference with treatments.

Mutation-Specific Notes (OTC): The standout mutation interaction here is PIK3CA – patients with PIK3CA-mutant tumors benefit dramatically from aspirin (as discussed)

www.oncnursingnews.com. If your tumor has a PIK3CA Q546K or M1043I mutation (both affect the PI3K pathway), aspirin is particularly worth discussing with your doctor given the strong evidence of benefit in that genetic context. In contrast, patients with tumors lacking those mutations may still take aspirin, but the expected benefit is smaller. APC mutations (like E1547*, E1374*, R216* in your list) and MUTYH mutations lead to activation of inflammatory pathways (COX-2 is often upregulated in APC-driven polyps). Thus, NSAIDs like aspirin can also help suppress polyp formation in APC-mutant contexts – in fact, FAP patients (who have APC mutations) had a significant reduction in polyp counts on aspirin in some studies (and definitely on sulindac/celecoxib as discussed later)pubmed.ncbi.nlm.nih.gov. There isn’t a specific vitamin or supplement tied to KRAS or SOX9 status. However, ensuring adequate vitamin D might be broadly beneficial, including for those with APC or KRAS mutations, as vitamin D can affect cell differentiation in the Wnt pathway (where APC and SOX9 function). Overall, the general OTC recommendations apply to all survivors, with aspirin being a notable “personalized” recommendation for PIK3CA-mutant cases.

Off-Label Prescription Medications

“Off-label” prescription approaches refer to medications that are approved for other conditions (diabetes, heart disease, etc.) or other diseases, but not specifically for colorectal cancer – yet have shown potential benefits in preventing cancer recurrence. These are experimental or repurposed strategies that one might consider with their oncologist’s guidance:

Metformin: Originally a diabetes medication, metformin has gained attention for its anti-cancer properties. It lowers blood glucose and insulin levels, which may starve insulin-sensitive tumors, and it activates AMPK, a cellular energy sensor that can inhibit cancer cell growth. Diabetic patients with colorectal cancer who happen to be on metformin have shown better outcomes on average than those on other diabetes medications

journals.plos.org. A pooled analysis indicated that metformin use was associated with improved survival and possibly lower recurrence in diabetic colon cancer patientsjournals.plos.org. Moreover, a phase II trial in non-diabetic individuals at high risk for colon cancer found metformin reduced formation of new adenomas by 40% vs placebo over 1 yearpmc.ncbi.nlm.nih.gov. Based on these data, metformin is being tested in clinical trials as an adjuvant therapy for colorectal cancer (to prevent recurrence). Some oncologists might consider prescribing low-dose metformin off-label for a survivor with prediabetes or other metabolic syndrome features, hoping to capitalize on its anticancer effect.

Research Quality: 4/5. Strong support comes from epidemiological and preclinical studies, and there are multiple small human trials (level 2–3 evidence) suggesting benefit. However, definitive phase III trial results in non-diabetic CRC survivors are not yet published (several are ongoing). Thus, evidence is promising but not yet level 5.
Side Effects: 2/5. Metformin is generally well tolerated. Common side effects are gastrointestinal (nausea, diarrhea) especially when starting, but these usually subside. It carries a very low risk of lactic acidosis (a rare but serious metabolic complication) in people with kidney impairment. Overall for a healthy individual, side effect risk is low. We score 2/5 because of the mild GI issues that some experience.
Effectiveness: 3/5. Likely a moderate effect in reducing recurrence risk, particularly for individuals with metabolic risk factors (obesity, high insulin) where metformin’s mechanism is most relevant. The expected benefit might be on the order of a 10-20% relative risk reduction in recurrence, based on observational data. This is meaningful but not as dramatic as, say, chemotherapy or aspirin in PIK3CA-mutant disease. Hence, metformin can be a helpful adjunct, though not a standalone guarantee. It is most often considered when there’s another reason to use it (e.g. borderline high blood sugar), making it a win-win.
Statins: Statin drugs (like atorvastatin, simvastatin), used for lowering cholesterol, have shown anti-cancer properties in lab studies – they can induce apoptosis in cancer cells and have anti-inflammatory effects. Some retrospective studies have found that colon cancer patients on statins had lower rates of recurrence and improved cancer-specific survival

academic.oup.com. For example, a meta-analysis of 23 studies found statin use was associated with about a 13% reduced risk of cancer recurrence (HR ~0.87)pmc.ncbi.nlm.nih.gov. However, not all studies agree, and a large randomized trial in the adjuvant setting (testing rosuvastatin in stage II/III colon cancer) unfortunately did not show a significant improvement in outcomes. The current thought is that statins might help certain subsets of patients (perhaps those with KRAS mutations or inflammatory tumors, since statins can inhibit some KRAS-driven pathways and reduce inflammation), but overall evidence is mixed. If a patient has high cholesterol or cardiovascular indications, using a statin might confer an added bonus for cancer prevention. But starting a statin purely for cancer prevention remains investigational.

Research Quality: 3/5. We have extensive human data from observational studies and some clinical trials, but results are inconsistent. This lands statins in moderate evidence territory – some signal of benefit but not definitively proven in a prospective trial for recurrence.
Side Effects: 2/5. Statins are widely used and generally safe. Possible side effects include muscle pain or weakness (in a minority of patients) and very rarely liver enzyme elevations or diabetes risk. There is an extremely low risk of serious muscle injury (rhabdomyolysis) in susceptible individuals. For most, these drugs are well tolerated. We rate 2/5 because side effects are usually mild and manageable.
Effectiveness: 2/5. Likely a small effect on recurrence risk. If benefit exists, it may be modest (perhaps a single-digit percentage improvement in recurrence-free survival). Statins are certainly not as potent as dedicated anti-cancer therapies in this context. That said, given their cardiovascular benefits, any slight cancer benefit is a bonus. Research is ongoing to identify if certain mutations (e.g. some RAS/RAF mutations) respond better to statin therapy; until then, the effectiveness for recurrence prevention is considered limited.
Mebendazole (Repurposed Antiparasitic): Mebendazole is a cheap anti-worm medication (for pinworm, etc.) that has shown surprisingly strong anti-cancer activity in preclinical studies. It disrupts microtubules in parasites – and similarly can inhibit cancer cell division. In cell culture and animal models, mebendazole slowed colon cancer growth and even enhanced the effect of certain chemotherapies

pmc.ncbi.nlm.nih.gov. While no large trials in humans have been completed yetecancer.org, there are remarkable case reports: one report described a patient with metastatic colon cancer who had exhausted standard treatments and was given mebendazole (100 mg twice daily). After 6 weeks, scans showed a near-complete remission of his lung and lymph node metastasesecancer.org. His liver metastases also shrank significantly. When the drug was paused, the cancer eventually progressed (with brain mets), suggesting mebendazole may have been controlling itecancer.org. Another case in a different cancer (adrenal cancer) likewise saw ~19 months of stable disease on mebendazole aloneecancer.org. These are anecdotes but very intriguing. Mebendazole is currently in early-phase trials for some cancers (e.g. a phase II for colon cancer adjuvant therapy is in development). Because mebendazole is off-patent and not a standard cancer drug, if one were to use it, it’s truly experimental and typically done only under trial or with physician oversight on a compassionate basis.

Research Quality: 2/5. Thus far, evidence is mainly preclinical and anecdotal. Lab studies (level 2) and case reports (level 1) suggest potential, but we lack controlled human trials demonstrating efficacy. The interest is high, and ongoing trials may raise this evidence level in the future.
Side Effects: 1/5. Mebendazole has been used in humans (including children) for decades for parasites and has low toxicity

ecancer.org ecancer.org. At the doses used for cancer (often similar to anti-parasite regimens, or somewhat higher but still within safe range), it’s usually well tolerated. Rarely it can cause liver enzyme elevations (as happened in the case report, reversible by dose adjustment)ecancer.orgor mild GI upset. It’s contraindicated in pregnancy. But overall, it’s one of the safer medications.
Effectiveness: 2/5. Unknown in a broad sense – we give it 2 because we only have a few cases of dramatic response. It’s not yet proven to consistently reduce recurrence. If those case outcomes were to generalize, it could be very effective, but until more data, we have to temper expectations. It might have a role in preventing regrowth of micrometastases if taken long-term, but that’s hypothetical at this point.
Celecoxib (and other NSAIDs) off-label: Celecoxib is a prescription COX-2 inhibitor (an NSAID) traditionally used for arthritis pain. It’s not “off-label” in the context of familial adenomatous polyposis (it’s actually FDA-approved to reduce polyps in FAP), but in an average colorectal cancer survivor, using celecoxib or other NSAIDs beyond aspirin could be considered off-label chemoprevention. Celecoxib has been shown to significantly reduce polyp counts in FAP patients – a 6-month trial in FAP reported about a 28-38% reduction in the number of colorectal polyps vs placebo

pubmed.ncbi.nlm.nih.gov www.cancernetwork.com. In sporadic cases, a large NIH trial (CALGB 80702) is examining whether 3 years of celecoxib after surgery and chemo improves disease-free survival; results are pending. The expectation is that celecoxib might help, especially in those whose tumors overexpress COX-2 (which is common in APC-mutant cancers). Because celecoxib can have cardiovascular side effects, it’s usually considered only if aspirin is not appropriate or if there are multiple polyps to manage. Another NSAID, sulindac, is also used in polyposis patients to prevent new polyps. In MUTYH-associated polyposis (MAP, caused by MUTYH mutations like E396* and G382D), patients often develop numerous polyps as well; clinicians might similarly use sulindac off-label to suppress polyp formation in the remaining colon/rectum. These NSAIDs essentially hold the polyposis in check and by extension may prevent new cancers, although they are adjuncts to endoscopic surveillance, not replacements.

Research Quality: 4/5. We have randomized trial evidence in polyp reduction (which is a surrogate for cancer prevention)

pubmed.ncbi.nlm.nih.gov. We also have extensive observational evidence that NSAID use correlates with less cancer. The only reason it’s not 5 is that long-term outcome trials for recurrence prevention are still underway.
Side Effects: 3/5. Chronic use of celecoxib or other NSAIDs carries risks: primarily gastrointestinal (ulcers, bleeding) and, for COX-2 selective like celecoxib, cardiovascular (increased risk of heart attack or stroke in susceptible individuals). In short 6-month polyp trials, celecoxib was well tolerated aside from minor GI complaints. But longer term, one must monitor blood pressure, kidney function, etc. We assign 3/5 because there are real risks, though manageable in many patients (especially if they have no serious cardiac history and maybe use gastroprotection).
Effectiveness: 4/5. In the context of polyp-formers (APC or MUTYH mutation carriers), NSAIDs can be very effective in reducing polyp burdenpubmed.ncbi.nlm.nih.gov, which likely translates to fewer chances for recurrence or new primaries. For an average patient, an NSAID like celecoxib might confer a similar benefit to aspirin (perhaps on the order of 20-30% risk reduction in recurrence), although this remains to be confirmed. We rate it 4 because in high-risk genetic cases it clearly reduces lesions, and it’s plausible it reduces recurrence in sporadic cases as well. However, its use needs to be individualized due to side effects.
Other Drug Repurposing Ideas: A few other off-label medications are being explored:
- Immune-modulators: For example, low-dose naltrexone (an opioid blocker) is theorized to boost immune surveillance at night when taken in low doses – only anecdotal evidence supports this, no solid trials yet (quality 1–2).
- Diabetes drugs like Acarbose: (starch blocker) or GLP-1 agonists for weight loss – by controlling glucose/insulin and obesity, they may indirectly lower cancer risk, but no direct evidence for recurrence (quality 2).
- Cimetidine: An old ulcer medication, had some small studies suggesting it might improve survival if given around the time of colon cancer surgery, possibly by enhancing immune response against the tumor. This is interesting but not widely adopted (quality 3, effectiveness 2). These are not standard, and their use would be experimental and case-by-case.

Mutation-Specific Insights (Off-label): Some of these repurposed drugs may be more relevant depending on tumor genetics. For instance, KRAS G12C mutation: There are actually new drugs designed for KRAS G12C (discussed in the next section) – but regarding repurposed meds, one observation is that tumors with KRAS or APC mutations often have upregulated COX-2/prostaglandin signaling. That suggests drugs like celecoxib (a COX-2 inhibitor) or even regular NSAIDs might be especially effective in those tumors by hitting a pathway they rely on. So an APC-mutant tumor or KRAS-mutant tumor might derive above-average benefit from NSAIDs/aspirin use. In contrast, a PIK3CA-mutant tumor might respond well to metformin because the PI3K pathway crosstalks with insulin/IGF signaling (metformin lowers insulin). Metformin and aspirin together might be quite powerful for a PIK3CA-mutant cancer, attacking two angles of that pathway. For MUTYH mutation carriers (MAP), the main concern is numerous polyps – so sulindac or celecoxib off-label is particularly relevant to them to prevent new tumors. SOX9 deletion (a Wnt pathway alteration) doesn’t point to a specific drug, but generally Wnt-driven cancers (APC, SOX9 are in the Wnt pathway) could potentially be sensitive to NSAIDs as well, since Wnt and COX-2 pathways cooperate in polyp formation. FGF23 R198W is a less common alteration (FGF23 is a hormone related to phosphate metabolism, not known to drive cancer), so it likely doesn’t change any drug recommendations. In summary, no off-label systemic medication is yet tailored exclusively to KRAS, APC, etc. for recurrence prevention – but understanding these mutations helps identify which repurposed drugs might target the tumor’s vulnerabilities (e.g. anti-inflammatories for Wnt pathway mutations, metabolic drugs for PI3K pathway mutations).

Prescription Medications (Standard Therapies to Reduce Recurrence)

This category includes the established medical treatments given to colorectal cancer patients after diagnosis to maximize cure rates and minimize recurrence, often as part of standard care or evidence-backed practice. These are typically prescribed by oncology and are considered part of the conventional treatment paradigm for appropriate stages or situations:

Adjuvant Chemotherapy: For patients with stage III (and high-risk stage II) colorectal cancer, standard practice is to administer chemotherapy after surgical removal of the tumor to eradicate microscopic residual disease. The most common regimen is FOLFOX (5-fluorouracil + leucovorin + oxaliplatin) or an oral equivalent like CAPOX (capecitabine + oxaliplatin). This treatment typically lasts 3 to 6 months post-surgery. Adjuvant chemo has a high-level evidence (level 5) of reducing recurrence and improving survival. For example, in stage III colon cancer, chemotherapy can reduce the risk of recurrence by roughly 30-40% and has been shown in large randomized trials to improve 5-year survival by about 15% or more compared to surgery alone

pmc.ncbi.nlm.nih.gov. Oxaliplatin-based chemo is the current standard, as it significantly improved outcomes over older regimens (like 5-FU alone or 5-FU with levamisole). Speaking of levamisole – it’s worth noting historically, Levamisole (a drug originally used in veterinary medicine for deworming) was part of the first effective adjuvant therapy (5-FU + levamisole) that showed improved survival in colon cancer in the 1990sar.iiarjournals.org. That has since been replaced by FOLFOX, but it underscores that many standard therapies have interesting origins in repurposed uses. Nowadays, all eligible patients receive modern chemo which is far more effective.

Research Quality: 5/5. This is supported by numerous large-scale human trials and meta-analyses over decades. The benefit of adjuvant chemotherapy for appropriate patients is indisputable (level 5 evidence).
Side Effects: 4/5. Chemotherapy is effective but comes with significant side effects. 5-FU/capecitabine can cause hand-foot syndrome, diarrhea, mouth sores, and lowered blood counts. Oxaliplatin causes neuropathy (nerve damage in hands/feet) in many patients, which can be long-lasting. There is also risk of infection due to neutropenia, fatigue, etc. Life-threatening complications are uncommon but can occur (neutropenic fever, severe allergic reaction, etc.). We rate 4/5 because side effects are common and sometimes severe, but they are generally manageable and usually temporary (except neuropathy in some cases). The risk of treatment-related death is low (~<1%), which is why we don’t score it 5 (which we reserve for something like a high-dose IL-2 type therapy with greater risk).
Effectiveness: 5/5. Adjuvant chemotherapy provides a major reduction in recurrence risk for those who need it. It can be the difference between cure and relapse in a substantial fraction of patients. For example, the 3-year disease-free survival might improve from ~60% with surgery alone to ~75% with chemo in stage III – a meaningful leap. Thus, it’s considered highly effective (one of the most powerful tools we have in preventing recurrence in resected colon cancer). All eligible patients are advised to undergo it, unless contraindicated by other health issues.
Targeted Therapies (for Residual Disease or Adjuvant Trials): In advanced/metastatic colorectal cancer, targeted drugs like anti-EGFR antibodies (cetuximab, panitumumab) for RAS wild-type tumors, or BRAF V600E inhibitors (in combination regimens), or immune checkpoint inhibitors for MSI-High tumors are used. In the context of recurrence prevention (adjuvant setting), these are not yet standard, but being researched. For instance, adjuvant trials of immune therapy (like nivolumab or pembrolizumab) in MSI-high colon cancers are underway given their huge success in metastatic disease – the idea is to mop up micrometastases in those genetically predisposed tumors. Similarly, specific mutations in your profile have corresponding targeted drugs:
- KRAS G12C: There are two oral KRAS G12C inhibitors approved in other cancers (sotorasib and adagrasib) that have shown activity in KRAS G12C-mutant colorectal cancer. In trials, these drugs have achieved partial responses in ~10% of CRC patients and disease control in more, although responses are less frequent than in lung canceraacrjournals.org. Researchers found combining a KRAS G12C inhibitor with an EGFR inhibitor significantly improved efficacy in CRC (since KRAS-mutant CRCs upregulate EGFR feedback). These combinations are in clinical trials. As of now, KRAS G12C inhibitors are not standard adjuvant therapy – one would typically only get them if the cancer recurred or metastasized. Using them prophylactically after curative surgery is untested. However, it is a potential future strategy once trials determine how well they work in minimal residual disease. If a patient has KRAS G12C and high risk of relapse, enrollment in a clinical trial (if available) with a KRAS G12C inhibitor could be considered.
- PIK3CA mutations: There are PI3K inhibitors (like alpelisib, approved in breast cancer) and mTOR inhibitors (everolimus) that target the PI3K pathway. These aren’t standard in colon cancer adjuvant therapy due to limited success in metastatic CRC thus far. But in theory, a PIK3CA-mutant tumor might be susceptible to such drugs. For example, everolimus was added in the aforementioned mebendazole case after progressionecancer.org, though without benefit. Currently, no PI3K inhibitor has proven value in CRC recurrence prevention.
- APC or Wnt-pathway mutations (including SOX9 deletion): Unfortunately, we have no approved targeted therapy for the Wnt signaling pathway aberrations (which are very common in CRC). This is an area of active research. Some experimental agents try to target beta-catenin or tankyrase, but none are in clinical use yet. So there’s no prescription medication specifically for APC or SOX9 mutant tumor suppression beyond the NSAIDs we discussed and standard chemo.
- MUTYH mutations: If you have biallelic MUTYH mutations (MUTYH-associated polyposis), the standard of care is surgical (remove polyposis if extensive) plus colonoscopic surveillance. As for meds: we mentioned NSAIDs like sulindac can reduce polyp formation in MAP patients as well. There’s no unique systemic therapy for MUTYH-defective tumors, but interestingly these tumors accumulate lots of oxidative DNA damage (G:C to T:A mutations); some researchers are looking at whether certain antioxidants or DNA repair modulators could help, but nothing concrete yet.
- FGF23 R198W (subclonal): FGF23 is not a typical oncogene in CRC; it might be a passenger mutation. There are drugs for FGFR family (FGFR inhibitors) used in other cancers (like bladder, cholangiocarcinoma), but FGF23 is a hormone, not a receptor, so this particular mutation likely isn’t targeted by any existing drug. No tailored therapy for that.
In summary, standard prescription targeted therapies in the adjuvant setting are currently limited to clinical trials. The only somewhat standard “targeted” agent in adjuvant therapy is oxaliplatin (which isn’t targeted to a mutation, but to rapidly dividing cells). We anticipate in the future, perhaps a KRAS-directed adjuvant trial or immunotherapy for MSI-high will become new standards if results are positive.

Research Quality: 5/5 (for standard chemo) and 3–4/5 (for newer targeted approaches). Adjuvant chemo is established by phase III trials (quality 5). Adjuvant targeted/immunotherapy is in trials (quality 3-4 currently).
Side Effects: 4–5/5 for chemo (significant side effects as described above), and 3/5 for most targeted therapies. For example, KRAS inhibitors can cause diarrhea, nausea, liver enzyme elevations, some electrolyte issues – generally manageable (grade 1-2 mostly) with a low risk of severe toxicity, so maybe side effect score 2-3 for them. Immunotherapies can cause immune-related side effects (colitis, hepatitis, etc.), which can be serious but are infrequent (maybe side effect score 3/5 for immunotherapy). Since this category covers a range, one would individualize the side effect profile to the drug in question.
Effectiveness: 5/5 for standard chemo (very effective as noted). For targeted agents like KRAS G12C inhibitors in metastatic disease, current effectiveness is modest (maybe 2/5 as single agent, though combos might improve that). In an adjuvant scenario, their effectiveness is unproven – theoretically, if even a small number of residual tumor cells are present, a targeted agent could eradicate them if the tumor is addicted to that pathway, but we don’t have data yet. Immune checkpoint inhibitors are extremely effective in MSI-H metastatic disease (many complete responses); if applied adjuvantly in MSI-H, effectiveness could be 5/5 (speculative). Since your mutations don’t include MSI markers, immunotherapy isn’t currently relevant. The main take-home is: follow standard chemo recommendations, and consider trials for any targeted agents if available.
Hormonal and Bone-Modifying Agents: While not directly “for CRC,” some patients (especially older women) may be placed on hormonal therapies like bisphosphonates or denosumab if they have osteoporosis after chemotherapy or due to menopause. Interestingly, an analysis of stage III colon cancer patients suggested those who took an osteoporosis drug (a bisphosphonate) had slightly improved disease-free survival, hinting at an anti-tumor effect on dormant cancer cells in bone. This is still exploratory – not a standard practice – but as a prescription measure, maintaining bone health with these agents has collateral potential benefit. Similarly, post-menopausal hormone replacement therapy has been associated with lower incidence of colon cancer in epidemiologic studies, but giving estrogen is not advised just to prevent cancer due to other risks.

Mutation-Specific (Prescription): The standard adjuvant chemo is recommended regardless of mutation status (with one exception: tumors with mismatch-repair deficiency (dMMR), which you did not list, generally do not benefit from 5-FU chemo in stage II – but for your listed mutations, that’s not applicable). If a tumor has a KRAS mutation (like G12C), one important point is that certain therapies (EGFR antibody drugs like cetuximab) would not be effective if the cancer ever recurred in metastatic form – so knowing that, doctors avoid those in KRAS-mutant cases. In terms of recurrence prevention, this means little now, but if a recurrence is detected, your treatment would be tailored knowing KRAS and PIK3CA status (e.g., possibly a trial of a KRAS inhibitor for KRAS G12C, or adding aspirin for PIK3CA as we discussed). For APC/MUTYH mutations: the standard prescription strategy is actually surgical and endoscopic – if someone had classic FAP (APC) or MAP (MUTYH) with dozens to hundreds of polyps, often a prophylactic colectomy is done to remove the at-risk colon entirely, which obviously prevents recurrence in that organ. In your case, multiple APC and MUTYH mutations in the tumor could hint at an underlying MAP condition; if confirmed, doctors would ensure any remaining colon/rectum is surveilled or removed to prevent new cancers. That’s more of a surgical intervention than a prescription, but it’s key for recurrence prevention in those genetic contexts. SOX9 deletion doesn’t alter standard treatment – it’s just another hit in the Wnt pathway like APC. There’s no specific extra therapy for that, so you’d follow the general recommendations.

To summarize this section: the cornerstone prescription intervention is completing the recommended chemotherapy and any indicated surgeries. These have the highest impact on preventing recurrence. Targeted and immunotherapies are exciting but mostly in the trial phase for adjuvant use. Always discuss with your oncologist about clinical trial options that might be suitable for your mutation profile – for example, trials adding a PI3K inhibitor for PIK3CA-mutant cancers or a KRAS G12C inhibitor trial. Outside of trials, focus on the proven therapies and combine them with the lifestyle and OTC measures for a holistic approach.

Potential Animal Drugs for Further Research

This section addresses unconventional approaches – drugs that are primarily used in veterinary medicine or are experimental, which have shown some anti-cancer activity in research. These are not standard of care but are sometimes mentioned in integrative oncology circles or are in early research phases for human cancer. They should be approached with caution and scientific skepticism until more data in humans emerge. Some notable examples:

Fenbendazole: Perhaps the most buzzed-about “animal drug” in cancer discussions, fenbendazole is a dog dewormer (antiparasitic) medication. It’s chemically related to mebendazole. In lab studies, fenbendazole has been found to inhibit cancer cell growth and induce cell cycle arrest in colorectal cancer cells and organoids

aacrjournals.org. It interferes with microtubules and glucose uptake in cancer cells, similar to mebendazole. However, the in vivo (animal) evidence is mixed. One study from researchers at Johns Hopkins/Yale tested fenbendazole in mouse tumor models and did not see a significant reduction in tumor growth in live mice when given at feasible dosespmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov, even though it did kill cancer cells at higher concentrations in the petri dish. This suggests fenbendazole might have bioavailability or dosing limitations in live organisms. Despite the limited animal efficacy data, there are numerous anecdotal stories of human patients (like a well-known case who publicized using fenbendazole for lung cancer) claiming it helped clear their cancer. These anecdotes are not verified clinical evidence – so currently, fenbendazole is considered unproven in humans. It is, however, very inexpensive and people sometimes use it on their own (which we do not recommend without medical supervision).

Research Quality: 2/5. We have preclinical studies (cell culture and some animal work) but no controlled human data. The evidence is at an early stage – promising in test tubes, but not yet convincingly effective in live animal models

pmc.ncbi.nlm.nih.gov. No trials in humans have been conducted, so it’s largely hypothesis-generating.
Side Effects: 2/5. In animals, fenbendazole is well tolerated (that’s why it’s a common dewormer). Humans have occasionally taken it short-term and generally did not report significant issues. Potential side effects might include liver function elevations or mild diarrhea, but serious toxicity isn’t well documented. Since it’s not an approved human drug, we give 2/5 due to the unknowns – likely low toxicity, but lacking formal safety studies in oncology patients (who may be on other meds).
Effectiveness: 1/5. So far, minimal evidence of effect in actual cancers in living subjects. The only hints of effectiveness are anecdotal, which cannot be relied upon. In rigorous tests, it did not shrink tumors in mice at standard dosingpmc.ncbi.nlm.nih.gov. It’s possible higher doses or combination with other therapies could show an effect, but as of now we must consider it unproven for real-world cancer control.
Ivermectin: Another antiparasitic that has crossed into cancer research. Ivermectin is used in humans for parasitic infections (e.g. river blindness) but is also a common veterinary dewormer. It has been shown to inhibit Wnt/β-catenin signaling – a pathway crucial in colorectal cancer (since APC mutations activate Wnt). Preclinical studies have demonstrated that ivermectin can induce apoptosis and arrest growth in colorectal cancer cell lines

pmc.ncbi.nlm.nih.gov. In mouse models, ivermectin slowed the growth of some tumors and even enhanced the effectiveness of certain chemotherapy drugsar.iiarjournals.org. It also may reduce cancer stem cell properties and metastasis potential (one study suggested ivermectin could inhibit metastasis through Wnt pathway modulatione-century.us). As of now, ivermectin has not been tested in clinical trials for colorectal cancer. There is some interest given its relative safety and the wealth of lab data.

Research Quality: 2/5. This rests on cell culture and animal studies (level 2). For example, ivermectin inhibited colon cancer cell proliferation in vitro and caused tumor cell death in mice

pmc.ncbi.nlm.nih.gov www.embopress.org. But we lack human trial data.
Side Effects: 1/5. Ivermectin is FDA-approved for humans (at specific doses for parasites) and is very well tolerated at those doses. In higher doses, it can cause symptoms like dizziness or mild neurological effects, but it has a wide safety margin. Given its extensive human use for other indications, it’s likely quite safe (score 1).
Effectiveness: 2/5. We see a potential effect in preclinical models, but no proven efficacy in preventing human cancer recurrence yet. It’s conceivable that ivermectin could be repurposed in the future (maybe combined with other treatments) if ongoing research pans out. At this time, effectiveness is speculative and probably low as a single agent.
Artemisinin Derivatives (e.g. Artesunate): Originally an anti-malarial (from the sweet wormwood plant), not exactly an “animal” drug but used in veterinary practice too for parasites. These have shown cancer-killing properties by generating free radicals in iron-rich cancer cells. A small pilot trial in colorectal cancer patients (in the UK) gave artesunate for two weeks before surgery and noted a trend to lower circulating tumor cells. It’s still very experimental. We mention it because it’s an example of a non-cancer drug showing some anti-cancer promise. Research Quality: 2/5 (early trials and lab studies), Side Effects: 1/5 (safe at anti-malarial doses), Effectiveness: 1–2/5 (no evidence for recurrence prevention yet, just an idea).
Dichloroacetate (DCA): This is a metabolic modulator used in some animal studies (and occasionally in veterinary or compassionate human use for metabolic disorders). It shifts cancer cell metabolism from glycolysis to glucose oxidation, potentially slowing tumor growth. Some case reports and small studies (in brain tumors, for instance) have been inconclusive. Quality: 2, Side Effects: 2 (can cause neuropathy), Effect: 1 (unproven in vivo).
Others (for further research): There are many interesting substances being tested at the fringes. For example, Newcastle disease virus (a bird virus) has been experimented as an oncolytic virus to infect and kill cancer cells – not mainstream, but in research. Benzimidazole compounds beyond fenbendazole (like others mentioned in the fenbendazole study) are being synthesized to better target hypoxic tumor cells

pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov. PSK (Polysaccharide-K) from turkey tail mushroom, though not an animal drug (it’s a biological product), has been used in Japan as an adjuvant therapy in colon cancer with some success in improving survivalwww.va.gov– it essentially acts as an immune booster. It’s worth noting that an immune stimulant from the veterinary world, Levamisole, as mentioned, was successfully repurposed in the 1990s for colon cancer (in combination with 5-FU)ar.iiarjournals.org. That provides proof that animal drugs can sometimes translate to real benefit in humans. Levamisole is no longer used due to side effects and better options, but it paved the way. Future research may identify similar repurposing wins.

Research Quality (Overall “Animal” Drug category): 2/5. On the whole, these strategies are backed by laboratory research and maybe some animal studies. They are at best in early clinical exploration. Thus, as a category, the evidence is low and predominantly preclinical.
Side Effects: 2/5. Most of these compounds (fenbendazole, ivermectin, artemisinins) are chosen partly because they have low toxicity in animals and humans at usual doses. So generally they are expected to be safe, but since they’re not standard, unexpected effects could occur or interactions with chemo could happen. We give 2/5 as an average – likely low side effects, but some unknowns (for instance, long-term use of fenbendazole in humans isn’t deeply studied; mebendazole data gives us confidence it’s low risk though

ecancer.org).
Effectiveness: 1/5. Currently, there is minimal evidence that any of these will significantly prevent recurrence in humans. If someone were to use one of these without other therapy, there’s no reliable data to show it would change the course of the disease. That said, they are promising leads for further research. It’s possible that in the future, one or more of these might earn a place as a supportive cancer therapy (e.g., perhaps ivermectin combined with chemotherapy to overcome drug resistance – an idea some researchers havewww.medsci.org). As of now, however, their effectiveness in practice is unproven, so we must score it low.

Conclusion: In minimizing colorectal cancer recurrence, a multifaceted approach is key. General recommendations – exercise, a healthy diet, maintaining healthy weight, and avoiding tobacco – form the foundation and benefit all survivors regardless of tumor genetics. On top of that, certain evidence-based interventions like aspirin (especially in PIK3CA-mutant cases) and vitamin D supplementation can be layered in, with generally low risk. Standard medical therapies (chemo and appropriate surgeries) are paramount and have the highest impact on preventing recurrence. Genetic mutations can inform some choices: for instance, aspirin for PIK3CA, NSAIDs for APC/MUTYH-related polyps, considering trials for KRAS G12C targeted drugs, etc., but they do not radically change the lifestyle advice – a KRAS-mutant survivor should still exercise and eat well, just as any survivor should. Lastly, while it’s fascinating to consider emerging and unconventional agents (from metformin to dog dewormers), these should complement – not replace – the proven strategies, and ideally be pursued in the context of clinical trials or with medical supervision. Each approach we reviewed comes with its own level of evidence, potential side effects, and degree of effectiveness, but when combined in a sensible way (and tailored to the individual), they offer the best chance of keeping colorectal cancer at bay.