Chemoprevention in familial adenomatous polyposis: past, present and future

Phillip M. Kemp Bohan*, Gautam Mankaney, Timothy J. Vreeland, Robert C. Chick, Diane F. Hale, Jessica L. Cindass, Annelies T. Hickerson, Daniel C. Ensley, Vance Sohn, G. Travis Clifton, George E. Peoples, Carol A. Burke

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

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.

Original languageEnglish
Pages (from-to)23-33
Number of pages11
JournalFamilial Cancer
Volume20
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Chemoprevention
  • Colorectal cancer
  • Familial adenomatous polyposis
  • Mammalian target of rapamycin
  • Rapamycin

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