Targeting mTOR signaling for the treatment of intrahepatic cholangiocarcinoma with TSC1/ARID1A mutations: a case report with an unexpected response

Ther Adv Med Oncol. 2024 Sep 13:16:17588359241271793. doi: 10.1177/17588359241271793. eCollection 2024.

Abstract

Biliary tract cancer incidence is increasing and the prognostic remains dismal. The development of personalized medicine is a pivotal issue in proposing therapeutic options for biliary tract cancer patients. Whole exome sequencing identifies approximately 15% of IDH1 mutations and 15% of FGFR2 fusions in intrahepatic cholangiocarcinoma. Other patients are not currently eligible for targeted therapy. Here, we present a patient treated for a metastatic cholangiocarcinoma with an unexpected response to a mammalian target of rapamycin (mTOR) targeting agent. Whole exome sequencing enabled the identification of TSC1 and ARID1A mutations. Reintroduction of mTOR inhibitors with similar results sustains the main role of these targeted agents in the control of the disease. These results suggest the existence of an mTOR oncogenic addiction in biliary tract cancer. Our results support the interest in performing exome sequencing in liver cancers and the potential to identify actionable mutations with important therapeutic issues.

Keywords: ARID1A; TSC1; case report; cholangiocarcinoma; mTOR inhibitors.

Publication types

  • Case Reports