A specific protein pair may be a prognostic biomarker for identifying smoking-related lung cancer, according to new research. The protein ASCL1 is associated with increased expression of the RET oncogene.
“This is exciting because we’ve found what we believe to be a ‘drugable target’ here,” said senior author George Vasmatzis, PhD, a molecular medicine researcher at the Mayo Clinic in Rochester, Minnesota. “It’s a clear biomarker for aggressive adenocarcinomas. These are the fast-growing cancer cells found in smokers’ lungs.”
The transcription factor ASCL1 is known to control neuroendocrine cell development. Previously, it was linked to regulation of thyroid and small cell lung cancer development, but not to smoking-related lung cancer.
The research found that the expression of ASCL1 occurred almost exclusively in smokers with adenocarcinoma, and not in nonsmokers or in other lung cancer subtypes. Tumors that were positive for ASCL1 expression had higher levels of RET, which is a known oncogene. The patients with high levels of the RET oncogene protein and tumors positive for ASCL1 that had did not survive as long as patients with high levels of RET and tumors that were not positive for ASCL1. Additionally, adenocarcinoma cells in which ASCL1 was silenced had markedly reduced cell growth and motility.
When researchers blocked the ASCL1 protein in lung cancer cell lines expressing both genes, the level of RET decreased and tumor growth slowed. The finding, combined with gene analysis, indicated that ASCL1 may be an upstream regulator of the RET oncogene. This information leads researchers to believe the mechanism will be a promising target for potential drugs and a strong candidate for clinical trials for the approximately 10% of cases of lung adenocarcinoma that are characterized by neuroendocrine differentiation.