Molecular pathways: protein methyltransferases in cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Protein methyltransferases (PMTs) are crucial enzymes catalyzing protein methylation.
• Histone methylation by PMTs regulates gene transcription and chromatin structure.
• Altered PMT activity is implicated in human cancers, creating dependencies in cancer cells.

Purpose of the Study:

• To review small-molecule inhibitors targeting specific PMTs.
• To discuss the therapeutic potential of PMT inhibitors in cancer treatment.
• To outline the current status of clinical trials for PMT inhibitors.

Main Methods:

• Review of scientific literature on PMTs and their inhibitors.
• Analysis of studies demonstrating selective killing of cancer cells by PMT inhibitors.
• Examination of clinical trial data for PMT inhibitors.

Main Results:

• Potent and selective small-molecule inhibitors of specific PMTs have been developed.
• These inhibitors effectively kill cancer cells with oncogenic alterations dependent on PMT activity.
• Selective inhibitors for DOT1L and EZH2 have advanced to Phase I clinical studies.

Conclusions:

• Targeting PMTs with selective inhibitors represents a promising personalized cancer therapeutic strategy.
• Clinical development of PMT inhibitors is progressing, with more agents expected in trials.
• PMT inhibitors offer a targeted approach to cancer treatment based on specific genetic dependencies.