NSAIDs
Cancer Medications
mTOR Inhibitors
Supplements & Diet
Additional Studies
Chemoprevention and Potential Anticancer Agents
Polyp Management
There currently are not any FDA approved medications to manage FAP in regard to preventing cancer. However, there are supplements and medications that have shown in studies to be helpful in reducing polyp growth in size or development and have off label uses for polyp management for FAP.
A difficulty with FAP studies and chemoprevention, is adverse events that are not well tolerated or toxicity concerns for long term use. Possible chemoprevention applicability for FAP has been discovered in other clinical treatment studies for other cancers. Both of these ends of the spectrum highlight the need for continued research and discussion of chemoprevention medication or supplements to better understand and improve the application for FAP patients.
NSAIDs
Sulindac
In studies with daily doses of 150-300 mg, reduction in polyp size and number of colorectal adenomas was shown. When used as a suppository, rectal polyps were reduced with significant reversion without polyp redevelopment during the treatment. However, when Sulindac was stopped rapid polyp growth occurred for both oral and suppository forms. Sulindac inhibits COX-1 and COX-2 enzymes which protect the stomach lining and promote inflammation, respectively. Due to this, some patients report negative side effects such as stomach pain and ulcers when taking Sulindac.
Celecoxib
In studies with 400 mg twice a day administration, colon polyp numbers and burden were significantly decreased, and duodenal polyps were also slowed in development. Celecoxib is a selective COX-2 inhibitor that works by blocking this enzyme, reducing inflammation. This is helpful as COX-2 is increased in colon adenomas and linked to the process of polyps developing cancerous cells.
Rofecoxib
Shown to reduce polyp formation but also raised blood clot events with prolonged use. Rofecoib is a COX-2 inhibitor that also works by blocking the COX-2 enzyme, thereby reducing inflammation.
Aspirin
Mixed results are shown in studies. Studies using 600 mg daily of aspirin showed some polyp size reduction and studies with 100mg daily dose showed significant reduction in recurring colorectal polyps, especially for those with AFAP. However, studies with aspirin have been complicated by GI adverse events from the aspirin making longer term studies difficult for further analysis.
Aspirin works as a COX inhibitor, irreversibly blocking COX-1 and COX-2 enzymes.
It’s important to note that Aspirin’s protective effects take approximately 5-10 years to begin.
When compared to mesalazine, another NSAID medication, aspirin showed to be more effective.
Indomethacin Suppositories
Studies using 50 mg once or twice daily showed a decrease in rectal polyp number in patients with an IRA. While polyp number did decrease, IHC test indicated there was increased cell proliferation in the biopsied rectal mucous membrane. Additionally, upon stopping the Indomethacin suppositories, polyp numbers increased again. Indomethacin works by blocking both COX-1 and COX-2 enzymes
Section Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC12127233/
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Cancer Medications
Erlotinib
In studies with 350mg once per week for 6 months, duodenal polyp burden was significantly reduced and a reduction in lower GI polyps was also seen. Erlotinib is an EGFR inhibitor, blocking pathways that drive cell proliferation and survival.
When Sulindac and Erlotinib were administered together in studies, a larger reduction in polyp burden was achieved together versus one by themselves.
Eflornithine
When Sulindac and Eflornithine were administered together in studies, the progression of lower GI disease in FAP was significantly delayed than when one medication was used by itself, particularly when post-hoc analysis was completed to look for secondary patterns and differences.
Eflornithine inhibits the ODC enzyme, which is necessary for cell growth and division. By inhibiting the ODC enzyme, cell division is slowed which can in turn slow cancer progression and reduce inflammation.
Imatinib
Shown to regress colorectal polyps. Imatinib works as a tyrosine-kinase inhibitor blocking BCR-ABL protein and c-KIT, PDGFR, and EphB receptors. Of particular interest for FAP, by blocking the EphB receptor from signaling, the cell proliferation during the earliest stages of tumor initiation are decreased in the intestinal epithelium layer. This layer serves as a key barrier against pathogens and coordinates essential digestive, immune, and metabolic functions.
BCR-ABL protein drives uncontrolled cell proliferation and survival.
c-KIT receptors act as a switch for cell proliferation, survival, and migration.
PDGFR receptors stimulate cell proliferation and plays significant roles in healing.
EphB receptors are crucial in guiding the development of cells and synapses for cell communication.
Venetoclax
Showed a reduced polyp number. Venetoclax works by inhibiting BCL-2 protein, which is overexpressed in early colorectal tumor development. BCL-2 protein is a cell survival protein that works to prevent cell death. In cancer, this overexpression of cell survival allows abnormal cells to continue to survive indefinitely.
Section Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC12127233/
mTOR Inhibitors
Rapamycin
Rapamycin, a mTOR inhibitor, showed reduced polyp size, number, and dysplasia for FAP patents. The mTOR protein helps to control several cell functions including proliferation and survival. mTOR inhibitors work by stopping the signal that tells cells to grow and divide, in cancer this helps to stop tumor growth.
eRapa
Another mTOR inhibitor; showed reduced polyp burden by working to inhibit the mTOR protein from excessive cell proliferation.
Section Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC12127233/
Supplements and Diet
Phytoestrogens
Phytoestrogens, plant derived compounds that have structures similar to estrogen, are found in foods such as soy, flaxseed, fruits, and vegetables. These foods can mimic or block the effect of estrogen on the body by binding to alpha and beta estrogen receptor cells. The Alpha estrogen receptors play a role in cell proliferation whereas ER β, Beta estrogen receptors, play a role in cell death. ER β is the predominant estrogen receptor in the normal colon epithelium, functioning as a tumor suppressor. ER β expression declines early on in the process of adenomas becoming cancerous.
When phytoestrogen foods were combined with insoluble fibers in studies, results showed the progression of polyps in FAP to reduce including in the colon and duodenum.
Vitamin C
Vitamin C was shown in some studies to provide a short-term improvement in reducing polyps but have not been sustained long term and its efficacy is suggested to be limited to those with KRAS mutations. Study participants that were given Vitamins C and E with high fiber, did show lower polyp numbers at specific time points in the study.
Vitamin C is an antioxidant that supports the immune system and protects cells from damage. Vitamin E is also an antioxidant protecting cells from damage, is supportive of the immune system and inflammation reduction.
Fish Oil (EPA-FFA form)
Fish oil, particularly in the EPA-FFA form, showed significant decreases in polyp size and number for those with remaining rectums or rectal parts. The EPA-FFA form of Fish oil works by reducing inflammation through inhibiting COX-2 receptor and mucosal arachidonic acid levels in organs.
Important Note – Fat soluble vitamins and supplements such as Vitamin E and Fish oil can cause health issues including organ damage as the body stores excess amounts of them in the liver and fatty tissues, limiting the body’s ability to properly flush out excess amounts out of the body.
Curcumin
Curcumin, when combined with quercetin, showed reduced polyp size and number. However, when taken alone at 1500mg twice daily, intestinal adenomas were not shown to be significantly affected.
When Curcumin was combined with piperine (black pepper), polyp regression was shown to occur.
Quercetin is an antioxidant that reduces inflammation and is immune supportive. It is present in piperine (black pepper), which increases quercetin’s absorption.
Curcumin is an antioxidant that targets several pathways in colorectal cancer including to reduce inflammation by inhibiting COX receptors and inhibiting cancer stem-like cell proliferation.
Black Raspberries (Suppository Form)
Black raspberries in suppository form showed in a trial to significantly reduce rectal polyp burden and a moderate reduction in number. Black raspberries are high in chemoprevention compounds including anthocyanins and ellagic acid. The suppository form showed to decrease uncontrolled cellular growth and division, decreased promotion of methylation of tumor suppressor genes and improved Wnt pathway regulation. As we discussed previously, methylation can silence genes such as the APC gene. By reducing the methylation and improved regulation of the Wnt pathway, the APC gene is able to increase its function as a tumor suppressor gene.
Section Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC12127233/
Additional Studies of Interest
Guselkumab (Tremfya)
Guselkumab (Tremfya) is a biologic medication used in chronic inflammatory diseases including IBD (Crohn’s disease and Ulcerative colitis). Guselkumab is an interleukin (IL)-23 inhibitor, blocking the IL-23 protein that is involved in inflammation as well as tumor growth in colorectal cancer. Pre-clinical models suggested promising results by decreasing inflammation and tumor development.
Erythromycin & Azithromycin
Erythromycin and Azithromycin are both Macrolides antibiotics to treat bacterial infections, although they are not the same antibiotic. They both work by not only preventing bacteria from growing but also have significant effects on reducing inflammation and improving immune system modulation.
A study using erythromycin showed a significant decrease in colon polyps.
In a mice study, results suggested Azithromycin to be a potential anticancer agent for FAP as it suppressed the number of small intestinal and cecum (part of the colon) tumors as well as the number of cancers originating from adenomas.
* Keep in Mind: It is important to discuss medications, supplements, and diet with your medical provider to determine the best course of action and any supplement/diet doses for you individually to prevent toxicity.
Education Resources
Empower Yourself – Learn from These Expert Resources
FAP & Me – A Guide to Familial Adenomatous Polyposis
A note to Parents
Welcome to “FAP & Me!” This booklet was written to reinforce the information about FAP that you, your doctors, and your genetic counselor have given your child. FAP & Me is useful in various ways, depending on the age of the child. Each child and family is different, and FAP & Me may have information that you have not shared with your child yet.
Please review FAP & Me to see whether the information is right for your child at this time. Your child may like reading FAP & Me with you, an older sibling, or another adult so that he or she can ask questions and have you explain things. We hope that FAP & Me is helpful!
– FAP & Me, a publication of the National Society of Genetic Counselors
A Patient’s Guide to FAP
The content in this guide is based on the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology “Genetic/Familial High-Risk Assessment: Colorectal” (2015).
This guide is intended to provide information for those affected by hereditary colon cancer syndromes and should not replace discussions or advice from your medical provider. We suggest you read this Guide in the order in which it is written, as each section builds upon information in previous sections. Medical terms in blue are explained in the glossary.
– paraphrased from ‘A Patient’s Guide to FAP’
Life’s a Polyp with Zeke and Katie
Yay, Yay DNA! Do You Wonder What Makes You You?
It’s all because of something called DNA.
What is DNA? It’s the instruction book for life. You have DNA. So do teeny little bugs, big elephants, tall trees, and colorful birds-every living thing has DNA! And you share DNA with just about every living thing on Earth. Join Mendel G. Cat and learn more about the tiny thin thread that connects all life.
– Mark A. Hicks
Shimmy the Shark and His Stoma