Why Some Lung Cancer Patients Stop Responding to Treatment
Published in Cancer Research, researchers have discovered why some patients with nonsmall cell lung cancer stop responding to treatment with tyrosine kinase inhibitors (TKIs): an epigenetic switch is flipped, reactivating genes that inhibit the effect of these drugs.
TKIs, specifically epidermal growth factor receptor inhibitors, are typically used to treat people with nonsmall cell lung cancer, a prevalent and usually incurable type of cancer that accounts for 80–85% of lung cancers. About 15–20% of these patients will become resistant to these standard treatments, resulting in their eventual death. This is because the cells develop a mutation that leads to resistance. But about half of the remaining resistant patients remain unexplained.
Cellular biologist Andrea Kasinski and her lab have found that the cause involves epigenetics. When cells lose a histone called methyltransferase (KMT5C), genes that KMT5C were repressing instead become expressed, leading to resistance to epidermal growth factor receptor inhibitors. This could open up development of new 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 poorly understood phenomenon.
“For the majority of genes that contribute to cancer, we’re not sure how they work yet,” Kasinski said. “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.”
Source: Purdue University
