Epigenetics likely to be the reason why lung cancer patients develop treatment resistance

Doctors typically treat people with nonsmall cell lung cancer, a prevalent and typically incurable type of cancer that makes up 80%-85% of lung cancers, with tyrosine kinase inhibitors, specifically epidermal growth factor receptor inhibitors. About 15%-20% of these patients will become resistant to these standard treatments, resulting in their eventual death.

Researchers understand part of the reason for this: The cells develop a mutation that leads to resistance. But about half of those resistant patients remain unexplained.

Andrea Kasinski, a cellular biologist, and her lab have discovered that some of the explanation is epigenetic. When cells lose the histone methyltransferase (KMT5C), genes that KMT5C were repressing instead become expressed, leading to resistance to epidermal growth factor receptor inhibitors.

This understanding lays the groundwork for future therapeutics and gives researchers and doctors a deeper insight into the biology and progression of cancers, especially the role that epigenetic-modifying proteins play in drug resistance, a phenomenon that is not well understood.

For the majority of genes that contribute to cancer, we're not sure how they work yet. And for many, we don't have a way to therapeutically target them. Research like this, that helps us understand how those genes work to determine cancer outcomes, adds to our understanding of the network. This knowledge will ultimately lead us to better therapeutics."

Andrea Kasinski, Cellular Biologist, Purdue University

Source:
Journal reference:

Pal, A. S., et al. (2022) Loss of KMT5C Promotes EGFR Inhibitor Resistance in NSCLC via LINC01510-Mediated Upregulation of MET. Cancer Research. doi.org/10.1158/0008-5472.CAN-20-0821

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