Which agents are used in the management of Peutz-Jeghers syndrome (PJS)?

Updated: Oct 11, 2018
  • Author: Buu Anh T To, MD; Chief Editor: Praveen K Roy, MD, AGAF  more...
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Chemopreventive strategies for familial adenomatous polyposis (FAP) syndrome management has led to investigation into cyclooxygenase (COX) inhibitors for Peutz-Jeghers syndrome (PJS). Rossi et al demonstrated that COX-2 was highly upregulated in a murine model of Peutz-Jeghers syndrome LKB1 mutant mice. [100] Polyps recovered from patients with Peutz-Jeghers syndrome also showed a significant correlation between LKB1 staining and COX-2, suggesting COX-2 is integral to the tumorigenesis pathway in Peutz-Jeghers syndrome. [101]

A decrease in polyp burden was reported in COX-2 knockout LKB-1 mutant mice, analogous to LKB-1 mutant mice treated with celecoxib. In that report of an uncontrolled, open-labeled pilot study in humans, Udd et al noted reduced gastric polyposis in patients treated with celecoxib. [102] Celecoxib use in Peutz-Jeghers syndrome, although promising, remains to be tested and currently cannot be routinely recommended in any age group.

Given that modulation of PI3-kinase is critical to the function of STK11 and, in turn, one of the major downstream mediators of PI3-kinase signaling is mammalian target of rapamycin (mTOR), inhibition of mTOR offers potential therapeutic possibilities in chemoprevention in Peutz-Jeghers syndrome. Rapamycin has been shown to be effective in reducing polyp burden in a murine model of Peutz-Jeghers syndrome. [103] In addition, RAD001 (everolimus) has been proposed as a potential chemopreventive agent and was reportedly effective in achieving a partial remission in a patient with Peutz-Jeghers syndrome with advanced pancreatic cancer. [104] Currently, the use of mTOR inhibitors is also not recommended as standard of care in adult and pediatric patients with Peutz-Jeghers syndrome.

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