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Aug 10, 2024;23 (1): 164.

Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions.

Hongyao Li, Xiang Wen, Yueting Ren, Zhichao Fan, Jin Zhang, Gu He, Leilei Fu
Author Information
  1. Hongyao Li: Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
  2. Xiang Wen: Department of Dermatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan University, Chengdu, 610041, China.
  3. Yueting Ren: Department of Dermatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan University, Chengdu, 610041, China.
  4. Zhichao Fan: Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
  5. Jin Zhang: School of Pharmaceutical Sciences of Medical School, Shenzhen University, Shenzhen, 518000, China. zhangjin1989@szu.edu.cn.
  6. Gu He: Department of Dermatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan University, Chengdu, 610041, China. hegu@scu.edu.cn.
  7. Leilei Fu: Institute of Precision Drug Innovation and Cancer Center, the Second Hospital of Dalian Medical University, Dalian, 116023, China. leilei_fu@163.com.
PMID: 39127670 DOI: 10.1186/s12943-024-02072-1

Abstract

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family.

Keywords

Cancer therapy Class I PI3K Clinical applications Molecular target PI3K family Small-molecule inhibitor Therapeutic approach

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MeSH Term

Humans
Neoplasms
Phosphoinositide-3 Kinase Inhibitors
Antineoplastic Agents
Animals
Molecular Targeted Therapy
Signal Transduction
Phosphatidylinositol 3-Kinases
Small Molecule Libraries
Protein Kinase Inhibitors

Chemicals

Phosphoinositide-3 Kinase Inhibitors
Antineoplastic Agents
Phosphatidylinositol 3-Kinases
Small Molecule Libraries
Protein Kinase Inhibitors
Journal Article Review
Article has an altmetric score of 3

Word Cloud

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