Navigating the interplay between BCL-2 family proteins, apoptosis, and autophagy in colorectal cancer

Colorectal cancer (CRC) remains a significant global health challenge, with an alarming upward trend in Asia. Early detection is crucial for improving outcomes, but there is no consensus on the optimal screening approach. Despite advances in diagnosis and therapy, CRC mortality rates remain substantial. Apoptosis and autophagy, key processes in cancer cell death, exhibit complex molecular crosstalk, particularly involving BH-3-only proteins, which present potential therapeutic targets. Recent studies suggest that manipulating these pathways could enhance cancer treatment by exploiting their regulatory networks. The B-cell lymphoma 2 (BCL-2) family proteins, central to apoptosis regulation, are implicated in CRC initiation, progression, and therapy resistance. BH3-only proteins like BIM and PUMA are linked to caspase-independent cell death, suggesting alternative pathways for CRC treatment and highlighting the potential for targeted therapies. This review provides an overview of CRC management, including the current landscape and challenges of screening programs and delves into the interplay between apoptosis and autophagy in CRC cell death. It emphasizes the critical role of BCL-2 family proteins in CRC pathogenesis and calls for future research to focus on developing non-invasive, cost-effective diagnostic biomarkers, establishing prognostic biomarker panels, and defining predictive biomarkers for existing treatments. These advancements are essential for improving screening strategies, therapeutic interventions, and ultimately, patient outcomes and quality of life.