Mechanisms and pathogenicity of the PI3K pathway: from basic research to clinical application

Abstract

PI3K signaling pathway is one of the most important signaling pathways in tumorigenesis. Dysfunction of PI3K signalling pathway has been widely found in lymphatic hematologic tumors and solid tumors. Different PI3K inhibitors have shown anti-tumor activity against a variety of tumors. Furthermore, the FDA has approved various PI3K inhibitors for marketing or clinical studies, and have achieved considerable efficacy, especially in lymphoma and breast cancer. However, drug resistance and treatment-related adverse reactions remain unsolved. The PI3K signaling pathway also involves several other physiological functions related signaling pathway networks, and the combination therapy of selective inhibition of these signaling pathways needs to be further explored. New strategies include the combination of allosteric inhibitors and orthosteric inhibitors of PI3Kα and the development of inhibitors of salvage mutation sites. This review summarizes the clinical research progress and common drug resistance mechanisms of various common malignancies involved in PI3K inhibitors. In addition to targeting cancer cells, PI3K inhibitors also have great potential in cancer immunotherapy in the future.