New genetic targets identified in small cell lung cancer
Small cell lung cancer (SCLC) is an extremely aggressive and lethal type of lung cancer. It accounts for about 10-15% of all lung cancers (about 30,000 people diagnosed each year), with only a 7% five-year survival rate. Current treatments for SCLC include radiation therapy and chemotherapy, but most patients quickly develop resistance to treatment; new, more effective treatments are desperately needed.
The biggest breakthrough in improved treatments for non-small cell lung cancer (NSCLC) has been the identification of driver mutations, specific genes that are mutated in NSCLC that cause tumor growth. Targeted therapies against these drivers (erlotinib and crizotinib) are a significant improvement over chemotherapy in patients whose tumors have these mutations. The hunt has been on for similar discoveries in SCLC.
New research published this week in Nature Genetics by two teams of researchers identified a number of new targets in SCLC through comprehensive genetic sequencing. The team led by UALC Medical Committee member Dr. Charles M. Rudin (Johns Hopkins) identified 22 significantly mutated genes, including genes in the SOX family, from 53 tumor samples.
The team confirmed TP53 and RB1 as the most commonly mutated genes in SCLC. However, they also found that about 27% of the samples had SOX2 amplification, meaning those tumors had more copies than usual of the SOX2 gene, and were able to identify a novel RFL-MYCL1 fusion, suggesting MYCL1 has a functional role in SCLC.
SOX2 is particularly interesting because of its link to stem cells, self-renewal, and embryonic development. In fact, SOX2 is one of a handful of genes needed to artificially reprogram normal cells into stem-like cells (called induced pluripotent cells or iPS cells). SOX2’s link to SCLC may give us new clues as to why SCLC is one of the most aggressive and lethal cancers, and why many patients suffer from rapid metastasis and experience relapse within two years.
This research points to some new therapeutic targets to investigate: SOX2, MYCL1, and the additional mutated genes identified in the study. Little progress has been made to date in the treatment of SCLC. This research gives us some new ideas and new paths to tread to develop new, more effective treatments.
UALC is currently funding a number of researchers studying SCLC, including Drs. Eric Haura, Lauren Byers and John Heymach, Julien Sage, Kwok-kin Wong, and others to continue to make progress against this disease. Follow the links above to read more about their research.