Strategies and techniques for preclinical therapeutic targeting of PI3Kin oncology: where do we stand in 2024?

INTRODUCTION The phosphatidylinositol-3-kinase (PI3K) pathway is a crucial intracellular signaling pathway involved in cell growth, proliferation, survival, and metabolism, which is aberrant in almost all types of cancer. Extensive research is dedicated to elucidating the mechanisms of action and developing PI3K inhibitors. However, only a small portion of the research has been successfully translated into clinical applications. AREAS COVERED In this review, we present an overview of the pivotal role that the PI3K pathway plays in tumor development. We discuss the current landscape of PI3K inhibitors in preclinical and clinical trials, address the mechanisms of resistance to PI3K inhibition along with their associated toxic effects, and highlight significant advancements in preclinical research of this field. EXPERT OPINION Based on our study and comprehension of PI3K, we provide a recapitulation of the key lessons learned from the research process and propose potential measures for improvement that could prove valuable.