Chemoprevention in familial adenomatous polyposis: past, present and future

• Published in: Familial cancer Vol. 20; no. 1; pp. 23 - 33
• Main Authors: Kemp Bohan, Phillip M., Mankaney, Gautam, Vreeland, Timothy J., Chick, Robert C., Hale, Diane F., Cindass, Jessica L., Hickerson, Annelies T., Ensley, Daniel C., Sohn, Vance, Clifton, G. Travis, Peoples, George E., Burke, Carol A.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-01-2021; Springer Nature B.V
• Subjects: Adenomatous Polyposis Coli - drug therapy; Adenomatous Polyposis Coli - prevention & control; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antibiotics, Antineoplastic - therapeutic use; Ascorbic Acid - therapeutic use; Aspirin - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Capsules; Celecoxib - therapeutic use; Chemoprevention - methods; Colorectal cancer; Colorectal carcinoma; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - therapeutic use; Drug Therapy, Combination - methods; Eflornithine - therapeutic use; Epidemiology; Erlotinib Hydrochloride - therapeutic use; Familial adenomatous polyposis; Fatty Acids, Nonesterified - therapeutic use; Genes, APC; Genetic disorders; Heredity; Human Genetics; Humans; Morbidity; Patients; Polyps; Rapamycin; Review; Sirolimus - therapeutic use; Sulindac - therapeutic use; Thyroid cancer; TOR protein; TOR Serine-Threonine Kinases - metabolism; Vitamins - therapeutic use; Rapamycin; Familial adenomatous polyposis; Chemoprevention; Mammalian target of rapamycin; Colorectal cancer
• ISSN: 1389-9600; 1573-7292
• DOI: 10.1007/s10689-020-00189-y

Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy and temporizing the development of extracolonic disease. An ideal chemoprevention agent should have a biologically plausible mechanism of action, be safe and easily tolerated over a prolonged treatment period, and produce a durable and clinically meaningful effect. To date, no chemoprevention agent tested has fulfilled these criteria. New agents targeting novel pathways in FAP are needed. Substantial preclinical literature exists linking the molecular target of rapamycin (mTOR) pathway to FAP. A single case report of rapamycin, an mTOR inhibitor, used as chemoprevention in FAP patients exists, but no formal clinical studies have been conducted. Here, we review the prior literature on chemoprevention in FAP, discuss the rationale for rapamycin in FAP, and outline a proposed clinical trial testing rapamycin as a chemoprevention agent in patients with FAP.