PI3K/AKT/mTOR-Targeted Therapy for Breast Cancer

Kunrui Zhu; Yanqi Wu; Ping He; Yu Fan; Xiaorong Zhong; Hong Zheng; Ting Luo

doi:10.3390/cells11162508

PI3K/AKT/mTOR-Targeted Therapy for Breast Cancer

Cells. 2022 Aug 12;11(16):2508. doi: 10.3390/cells11162508.

Authors

Kunrui Zhu^{1

2}, Yanqi Wu¹, Ping He^{1

2}, Yu Fan², Xiaorong Zhong^{1

2}, Hong Zheng^{1

2}, Ting Luo^{1

2}

Affiliations

¹ Breast Disease Center, Cancer Center, West China Hospital, Sichuan University, Chengdu 610000, China.
² Multi-Omics Laboratory of Breast Diseases, State Key Laboratory of Biotherapy, National Collaborative, Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610000, China.

Abstract

Phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) (PAM) pathways play important roles in breast tumorigenesis and confer worse prognosis in breast cancer patients. The inhibitors targeting three key nodes of these pathways, PI3K, AKT and mTOR, are continuously developed. For breast cancer patients to truly benefit from PAM pathway inhibitors, it is necessary to clarify the frequency and mechanism of abnormal alterations in the PAM pathway in different breast cancer subtypes, and further explore reliable biomarkers to identify the appropriate population for precision therapy. Some PI3K and mTOR inhibitors have been approved by regulatory authorities for the treatment of specific breast cancer patient populations, and many new-generation PI3K/mTOR inhibitors and AKT isoform inhibitors have also been shown to have good prospects for cancer therapy. This review summarizes the changes in the PAM signaling pathway in different subtypes of breast cancer, and the latest research progress about the biomarkers and clinical application of PAM-targeted inhibitors.

Keywords: AKT; PI3K; biomarker; breast cancer; cancer therapy; mTOR.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Breast Neoplasms* / drug therapy
Breast Neoplasms* / metabolism
Female
Humans
Molecular Targeted Therapy
Phosphatidylinositol 3-Kinase / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins c-akt* / metabolism
TOR Serine-Threonine Kinases / metabolism

Substances

Biomarkers
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors
MTOR protein, human
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases

Grants and funding

This research was funded by the Key Research and Development Project of Science and Technology Department of Sichuan Province, grant number 00402053A2231 and the 135 project for disciplines of excellence, West China Hospital, Sichuan University, grant number: ZYGD18012.