Targeting PRMT5 in cancer: Mechanistic insights and clinical progress

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• Arginine methylation is a critical regulatory mechanism in cancer.
• Protein arginine methyltransferase 5 (PRMT5) catalyzes arginine methylation.
• PRMT5 dysregulation promotes malignant transformation and disease progression.

Purpose of the Study:

• To review the oncogenic functions of PRMT5.
• To highlight emerging therapeutic strategies targeting PRMT5.
• To discuss the role of PRMT5 in cancer survival, proliferation, metastasis, and resistance.

Main Methods:

• Review of current scientific literature on PRMT5 in cancer.
• Analysis of PRMT5's molecular mechanisms and substrates.
• Evaluation of PRMT5 inhibitor development and clinical efficacy.

Main Results:

• PRMT5 influences chromatin organization, RNA metabolism, and oncogenic signaling.
• Elevated PRMT5 expression is linked to multiple cancer types and poor prognosis.
• Early PRMT5 inhibitors showed limited efficacy, while MTA-cooperative inhibitors demonstrate enhanced selectivity in MTAP-deleted tumors.

Conclusions:

• PRMT5 is a significant driver of cancer, making it a promising therapeutic target.
• Targeting PRMT5, particularly with MTA-cooperative inhibitors in MTAP-deleted cancers, represents a key advance in precision oncology.
• Further research is needed to optimize PRMT5 inhibition strategies and combination therapies for improved cancer treatment.