One Large Step in the Small-Cell Lung Cancer Journey

Small cell lung cancer has higher levels of PARP1 and EZH2.

(RxWiki News) There are two major types of lung cancer. The most common type is called non-small cell lung cancer. Small cell lung cancer makes up only about 15 percent of the 226,000 cases of lung cancer diagnosed in the US every year. New treatments for this more aggressive lung cancer may be on the horizon.

Researchers have found two possible targets that drugs could attack to treat people with small cell lung cancer.

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Investigators at The University of Texas MD Anderson Cancer Center uncovered the new targets known as PARP1 and EZH2.

“Unlike non-small cell lung cancer [NSCLC], where there have been new targeted drugs developed in the last ten years, the only currently approved treatments for small cell lung cancer are cytotoxic chemotherapies,” said Lauren A. Byers, MD, assistant professor of thoracic/head and neck medical oncology at MD Anderson.

“Because most targeted therapies directly act on proteins, identifying if certain proteins are overexpressed in small cell lung cancer could have therapeutic applications,” Dr. Byers said.

Researchers studied the expression – or levels – of about 200 proteins that are known to be involved in lung cancer.

The scientists wanted to see how the two types of lung cancer differed in their molecular makeup.

Dr. Byers said that NSCLC and small cell lung cancer “have dramatically different protein profiles in terms of which proteins are ‘turned on’ and are driving the behavior of these cancers.”

In small cell, researchers found higher levels of two proteins that are designed to help DNA repair itself: PARP1 and EZH2.

New drugs targeting PARP1 are in late stage clinical trials for other cancers, including breast and ovarian.

“The possibility that DNA repair could be one such Achilles’ heel and that PARP inhibitors, drugs which are already in clinical trials, could target this area is very promising, said D. Ross Camidge, MD, PhD, the director of the lung cancer clinical program at University of Colorado Hospital. Dr. Camdige was not involved in this study.

Small cell lung cancer is sensitive to platinum-based chemotherapy. Researchers looked at how two PARP inhibitors worked with standard of care chemotherapy – cisplatin and etoposide (both of which are platinum-based), and another chemo agent called irinotecan.

The experimental drugs slowed down the growth of small cell lung cancer cells.

“Although this is early data and only in vitro [cells] data, small cell has been crying out for any kind of molecular lead to chase down,” said Dr. Camidge.

“Our next step is to begin to examine the use of PARP inhibitors in combination with other drugs in preclinical and clinical investigations of small cell lung cancer,” Dr. Byers said.

“The goal will be to generate clinical data as soon as possible, in both the platinum sensitive and platinum resistant settings,” Dr. Camidge said.

“The great anticipation of really seeing if this work is going to open up a whole new realm in small cell therapy is a testament to how much we need a breakthrough in this disease."

This study was published September 6 in Cancer Discovery, a journal of the American Association for Cancer Research.

This work was supported by The University of Texas Southwestern Medical Center and The University of Texas MD Anderson Cancer Center Lung SPORE; DoD PROSPECT AACR-AstraZeneca-Prevent Cancer Foundation Fellowship for Translational Lung Cancer Research; MD Anderson Cancer Center Physician Scientist Award; Barbara Rattay Advanced Fellowship Program, Chapman Fund for Bioinformatics in Personalized Cancer Therapy and the E.L. Wiegand Foundation.

Two of the authors disclosed financial relationships with pharmaceutical companies, among them Amgen, Astra-Zeneca, GlaxoSmithKline and Wyeth/Pfizer. The other authors reported no conflicts of interest.

Review Date: 
September 6, 2012