# MDM2 as a therapeutic target in advanced biliary tract cancers

## TL;DR

This paper reviews the role of MDM2 in biliary tract cancers and its potential as a target for new therapies.

## Contribution

The paper provides a comprehensive review of MDM2's emerging role as a therapeutic target in biliary tract cancers.

## Key findings

- MDM2 amplification is observed across all biliary tract cancer subtypes.
- MDM2 inhibition may restore p53 tumor suppressor function in BTCs.
- Current understanding of MDM2's role in BTC pathogenesis is still evolving.

## Abstract

Biliary tract cancers (BTCs) are a heterogeneous group of tumors arising from cells in the bile ducts and gallbladder. The 5-year overall survival rate for all BTC stages combined is ~20%, and treatment options for patients with unresectable disease are limited, leaving an unmet clinical need. In recent years, significant efforts have been made to refine and implement targeted therapeutic approaches for patients with BTC. The adoption of early and comprehensive molecular profiling is crucial to identifying patients who may be candidates for effective targeted therapies. Characterization of the molecular landscape of BTCs led to the identification of murine double minute 2 homolog gene (MDM2) amplification across all BTC subtypes. The MDM2 protein is a critical negative regulator of p53 stabilization and activity that is an emerging actionable biomarker in BTCs. There are multiple therapeutic approaches that aim to target MDM2 activity, thereby restoring the intrinsic tumor suppressor function of p53 and halting oncogenesis. However, these have been limited by our evolving understanding of the role of MDM2 in BTC pathogenesis. Here, we offer a review of the current understanding of the role of MDM2 in BTC biology and its therapeutic implications.