Small-cell lung cancer breakthrough: MicroRNAs key to identifying patients resistant to 'first-line' chemotherapy

The study, Tumor MicroRNA Biomarkers Associated with De Novo Chemoresistance in Small Cell Lung Cancer, are being presented in San Diego at a joint conference of the American Association for Cancer Research (AACR) and the International Association for the Study of Lung Cancer (IASLC).

This breakthrough is critical since patients with small-cell lung cancer (SCLC) often do not get a second chance at therapies to combat this aggressive type of cancer.

"For patients with small cell lung cancer, there are really only about two chemotherapy options. We need to be more precise with our treatments and identify who is going to be resistant up front in order to design better clinical trials that will identify effective therapies for these at-risk patients," said Dr. Glen J. Weiss, director of Thoracic Oncology at TCRS, who presented the findings at AACR-IASLC's Joint Conference on Molecular Origins of Lung Cancer.

TCRS is a partnership between the Translational Genomics Research Institute (TGen) and Scottsdale Healthcare that enables laboratory discoveries to be quickly turned into targeted therapies that can be tested with patients at the Virginia G. Piper Cancer Center in Scottsdale.

Of the nearly 32,000 new cases of SCLC diagnosed in the U.S. every year, between 15 and 30 percent will be chemoresistant to first-line therapy, or about 6,500 SCLC patients annually. SCLC tends to spread much more quickly than non-small cell lung cancer. There are three types of SCLC: small cell carcinoma (oat cell cancer), mixed small cell/large cell carcinoma, and combined small cell carcinoma.

The study led by Dr. Weiss proposed to look at how to best identify those SCLC patients who would be chemoresistant. By profiling tumors, he and a team of TGen researchers identified at least three tumor microRNAs that appear to predict small cell lung cancer patients who will prove resistant to first-line chemotherapy. In addition to researchers at TGen, Dr. Weiss was assisted by scientists at the Scottsdale Clinical Research Institute and the Van Andel Research Institute.

MicroRNAs are small molecules that regulate gene expression in the process of making proteins as well as directing the structure and function of cells. This regulation usually prevents cancer and other diseases.

Weiss and colleagues evaluated 34 patients at with varying stages of SCLC. The median age of the patients was 69.1 years, and half were men. All 34 received systemic chemotherapy. There were two complete responses and 13 partial responses. Two patients had stable disease and four had progressive disease.

Three microRNAs biomarkers were identified as being closely linked with chemoresistance: miR-92a-2*, miR-147, and miR-574-5p. Although 47 percent of the patients presented with hypertension and 32 percent presented with emphysema or chronic obstructive pulmonary disease, neither of these co-morbidities were linked with chemoresistance.

These findings should help clinicians design better drug trials.

Dr. Weiss has received grant funding to support this work from these charitable organizations: Sylvia-Chase Foundation, American Cancer Society, IBIS Foundation of Arizona, and the TGen Foundation.