# BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting

## TL;DR

This review discusses how BCL-2 and BCL-xL proteins contribute to cancer and explores strategies to target them for treatment.

## Contribution

The paper provides a comprehensive overview of the regulation, function, and therapeutic targeting of BCL-2 and BCL-xL in cancer.

## Key findings

- BCL-2 and BCL-xL promote cancer progression by enhancing invasiveness and drug resistance.
- These proteins have non-apoptotic roles in metabolism and mitochondrial dynamics.
- BH3 mimetics and combination therapies are being tested to inhibit BCL-2 and BCL-xL in cancer treatment.

## Abstract

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellular responses to chemotherapy, often conferring drug resistance. Additional non-apoptotic functions, including roles in metabolism, mitochondrial dynamics, and cellular homeostasis, further expand their biological relevance. Clinical trials exploring strategies to inhibit BCL-2 and BCL-xL, including selective BH3 mimetics and combination regimens, are discussed with emphasis on their potential and limitations in oncology. Overall, this review highlights the multifaceted contributions of BCL-2 and BCL-xL to cancer biology and underscores the importance of continued efforts to refine targeted therapeutic approaches.