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ASCL1 and NEUROD1, new therapeutic targets for small cell lung cancer


Researchers at UT Southwestern Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer and that, when deleted in the lungs of mice, prevents the cancer from forming.

The new findings identify ASCL1 as an important therapeutic target for small cell lung cancer, for which there have been few changes in treatment for the past 30 years.

Researchers have used a genetically engineered mouse model that develops human-like small cell lung cancer and identified two regulatory pathways that in turn revealed vulnerabilities in this cancer.

The findings, published in the journal Cell Reports, are important because survival for patients with small cell lung cancer is poor and few therapies are available.

Small cell lung cancer is a devastating disease that is diagnosed in 30,000 people a year in the U.S. and accounts for roughly 15% of lung cancer cases.
Most patients survive one year or less and therapy has not changed significantly in 30 years.
This work shows the possibility of developing entirely new types of targeted therapies for small cell lung cancer by focusing on ASCL1.

Signs and symptoms of small cell lung cancer include coughing, shortness of breath, and chest pain, and the rapid development of widely spread disease around the patient's body.
Smoking is the major risk factor for small cell lung cancer according to the National Cancer Institute ( NCI ), which helped fund the study along with the Cancer Prevention and Research Institute of Texas.

The team of researchers determined that the ASCL1 protein found in most small cell lung cancer tumors is required for formation of the disease.
When researchers deleted ASCL1 in the lungs of mice genetically engineered to develop small cell lung cancer, this loss prevented development of the cancer.

Additionally, researchers were able to differentiate between the tumor-promoting function of ASCL1 and a related protein, NEUROD1, in small cell lung cancer.
Some small cell lung cancers expressed ASCL1 whereas others expressed NEUROD1, and although the two genes regulate different processes in the cells, both appear to control genes that are important in driving this cancer.

Source: UT Southwestern Medical Center, 2016

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