A study presented at the Molecular Origins of Lung Cancer Conference found that three tumor microRNAs appear to predict when first-line chemotherapy will fail in some patients with small cell lung cancer, a problem affecting approximately 6500 patients annually. “For patients with small cell lung cancer, there are really only about two [platinum- based] chemotherapy options. We need to be more precise with our treatments and identify earlier who is going to be resistant in order to design better clinical trials that will identify effective therapies for these at-risk patients,” said Glen J. Weiss, MD, lead investigator of the study and director of thoracic oncology at the Virginia G. Piper Cancer Center at Scottsdale Healthcare and co-head of the Lung Cancer Unit at the Translational Genomics Research Institute (TGen), in a press statement.
The study included 34 patients (median age, 69.1 years) with small cell lung cancer in various stages. Following systemic chemotherapy, there were two complete responses and 13 partial responses. Two patients had stable disease and four had progressive disease. Weiss and colleagues conducted microRNA assessments to understand chemoresistance in these patients. MicroRNAs were chosen because they regulate gene expression similar to messenger RNA, but are smaller and more stable across a variety of fluid and tissue types.
The initial assessment found 16 microRNAs associated with progressive disease, and further testing identified three microRNAs linked to chemoresistance, including miR-92a-2 (P = .010), miR-147 (P = .018), and miR-574-5p (P = .039). These findings were validated by quantitative real-time polymerase chain reaction. Weiss noted that although 47% of patients had hypertension and 32% had emphysema or chronic obstructive pulmonary disease, these comorbidities were not linked to chemoresistance.
The microRNA biomarkers identified by Weiss and colleagues will have to be evaluated in an independent cohort of small cell lung cancer patients before any patient will be denied chemotherapy based on these findings, noted Tyler Jacks, PhD, president of the AACR, during the media briefing. Thereafter, studies will need to be conducted to determine what therapies may be effective in patients with chemoresistance. The hope is that this fi nding will help personalize treatment in patients with small cell lung cancer, a disease that has not seen any real treatment advances in well over a decade.