Phosphatidic acid as a cofactor of mTORC1 in platinum-based chemoresistance: Mechanisms and therapeutic potential

被引：2

作者：

Alizadeh, Hadi ^{[1
]}

Kerachian, Sana ^{[1
]}

Jabbari, Keyvan ^{[1
]}

Soltani, Bahram Mohammad ^{[1
]}

机构：

[1] Tarbiat Modares Univ, Fac Biol Sci, Dept Mol Genet, Tehran 14115 154, Iran

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2025年 / 988卷

关键词：

Platinum-based chemoresistance; mTORC1; Phosphatidic acid; mTOR inhibitors; ADVANCED SOLID TUMORS; PHOSPHATIDYLINOSITOL 3-KINASE PI3K; CANCER CELL-PROLIFERATION; ADVANCED BREAST-CANCER; 1ST-IN-HUMAN PHASE-I; BETA LPAAT-BETA; DOSE-ESCALATION; OVARIAN-CANCER; CISPLATIN RESISTANCE; HEPATOCELLULAR-CARCINOMA;

D O I：

10.1016/j.ejphar.2024.177220

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Platinum-based chemotherapeutics, such as cisplatin and carboplatin, are widely used to treat various malignancies. However, the development of chemoresistance remains a significant challenge, limiting their efficacy. This review explores the multifaceted mechanisms of platinum-based chemoresistance, with a particular focus on the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which plays a critical role in promoting tumor survival and resistance to platinum compounds. Additionally, we examined the role of phosphatidic acid (PA) and its synthesizing enzymes, phospholipase D (PLD) and lysophosphatidic acid acyltransferase (LPAAT), in the regulation of mTORC1 activity. Given the involvement of mTORC1 in chemoresistance, we evaluated the potential of mTOR inhibitors as a therapeutic strategy to overcome platinum resistance. Finally, we discuss combination therapies targeting the mTOR pathway alongside conventional chemotherapy to improve treatment outcomes. This review highlights the potential of targeting mTORC1 and related pathways to improve therapeutic strategies for chemoresistant cancers.

引用

页数：19

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