A Yale-led study describes how a known cancer gene, EGFR, silences genes that typically suppress tumours.

The finding, published in Cell Reports, may lead to the development of more effective, individualised treatment for patients with lung cancer and other cancer types.

Mutations in the EGFR gene are linked to multiple cancer types, including cancers of the lung, brain, and breast.

Yet scientists did not know precisely how EGFR represses genes that prevent cancers.

The Yale team conducted multiple experiments and found that EGFR silences tumour suppressor genes in lung cancer and glioblastoma, a type of brain cancer.

"EGFR can target multiple unrelated tumour suppressor genes in different cancer types using a common mechanism," said senior author Narendra Wajapayee, assistant professor of pathology and a member of Yale Cancer Center. EGFR silences these genes by negatively regulating a protein called TET1, which is required to suppress tumours, he noted.

"Our study suggests that TET1 determines the response to EGFR TKIs because the loss of TET1 expression confers resistance to EGFR TKIs. Collectively, these results demonstrate that oncogenic EGFR-mediated epigenetic silencing and regulation of DNA demethylase is central to the role of EGFR as an oncogene and determines the cellular response to EGFR TKIs" the paper concludes.

The finding informs the future direction of research and treatment of patients who don't respond or develop resistance to drugs that inhibit EGFR, he said. "It will also help determine how effective cancer therapies will be against different EGFR mutations."

Source: Cell Reports