Chemoprevention in familial adenomatous polyposis: past, present and future
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REVIEW
Chemoprevention in familial adenomatous polyposis: past, present and future Phillip M. Kemp Bohan1 · Gautam Mankaney2 · Timothy J. Vreeland1 · Robert C. Chick1 · Diane F. Hale1 · Jessica L. Cindass1 · Annelies T. Hickerson1 · Daniel C. Ensley3 · Vance Sohn4 · G. Travis Clifton1 · George E. Peoples5 · Carol A. Burke2 Received: 19 February 2020 / Accepted: 18 May 2020 © This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2020
Abstract 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. Keywords Familial adenomatous polyposis · Chemoprevention · Rapamycin · Mammalian target of rapamycin · Colorectal cancer
Introduction Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary colorectal cancer (CRC) syndrome characterized by the development of innumerable colorectal * Phillip M. Kemp Bohan [email protected] 1
Department of Surgery, Brooke Army Medical Center, 3551 Roger Brooke Dr., Ft Sam Houston, TX 78234, USA
2
Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA
3
Department of Urology, Brooke Army Medical Center, Ft. Sam Houston, TX, USA
4
Department of Surgery, Madigan Army Medical Center, Joint Base Lewis-McChord, Tacoma, WA, USA
5
Cancer Vaccine Development Program, San Antonio, TX, USA
adenomas. The incidence of this syndrome is approximately 1 in 8300, with onset typically in the second or third decade of life [1]. FAP results from a germline pathogenic variant in the adenomatous polyposi
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