Safety Study for the Use of Rapamycin in Children With Familial Adenomatous Polyposis

FAP is a rare genetic disease linked to mutations of APC gene. Adenomatous polyps appear around the age of 10 and will evolve into colic adenocarcinoma. To date, there is no effective treatment; 100% of patients will develop colorectal cancer before 40 years. This risk is addressed by regular colonoscopy monitoring, in order to propose a timely prophylactic colectomy. Rapamycin (sirolimus) is a drug that targets the mTOR (mammalian target of rapamycin) protein involved in the PI3K-Akt signalling pathway downstream of PI3K. There are interactions between the PI3K-Akt pathway and the Wnt/APC/-catenin pathway that is hyperactivated in FAP. Rapamycin was used out of indication with efficacy and good tolerance in 2 adolescents whose parents had refused colectomy. Researchers recently demonstrated its effectiveness in a child with very severe juvenile polyposis. Data are also available in animals, but no proof-of-concept studies have been conducted in humans. In France, Rapamycin use is allowed in adults with kidney transplantation and pulmonary lymphangioleiomyomatosis. However, it is used on children over the market. According to the literature and the field experience, the hypothesize is that a through level of 3-8 ng/ml should be effective in children with FAP, with a lower rate of adverse events.