PIK3CA in Cancer: Structure, Biology, Alterations, and Actionability

Abstract

Simple Summary PIK3CA is one of the most frequently altered cancer-related genes and has become an important focus of precision oncology. However, the biological and clinical implications of PIK3CA alterations vary considerably across tumor types, and translating this knowledge into effective treatments remains challenging. This review provides a comprehensive, updated, and comparative overview of PIK3CA biology, its molecular alterations across human cancers, their prognostic and therapeutic relevance, and the current development of treatments targeting the pathway activated by PIK3CA. We critically examine both established evidence and remaining limitations, including treatment toxicity and resistance, and discuss emerging therapeutic and molecular approaches. By bringing these different aspects together, we aim to provide oncologists and researchers with a practical framework for understanding the current state of the field, interpreting available evidence, identifying unresolved questions, and designing future clinical and translational studies.