Doctors commonly use tyrosine kinase inhibitors, particularly epidermal growth factor receptor inhibitors, to cure patients with non-small cell lung cancer, a common and typically deadly kind of cancer that accounts for 80% to 85% of lung cancers. About 15% to 20% of these individuals will develop resistance to these routine treatments, leading to their demise.
Half the reason for this, according to researchers, is that the cells develop a mutation that causes resistance. However, roughly half of the resistant patients have no known the cause. Andrea Kasinski, a cellular biologist, and her team observed that epigenetics plays a role in several of the explanations. When cells lose the histone methyltransferase (KMT5C), genes that KMT5C was suppressing become transcribed instead, resulting in resistance to EGF receptor inhibitors.
This knowledge paves the way for future therapies and gives scientists, and doctors a better understanding of cancer biology and evolution, particularly the function of epigenetic-modifying proteins in drug resistance, a poorly known phenomenon.
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, which 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
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.