Molecular Differences ID'd for Small/Non-Small Cell Lung CA
Small cell lung cancers have high expression of PARP1; are more sensitive to PARP inhibition
TUESDAY, Sept. 11 (HealthDay News) -- Molecular differences have been identified in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines, which may represent potential therapeutic targets, according to a study published online Sept. 6 in Cancer Discovery.
Lauren Averett Byers, M.D., of the University of Texas MD Anderson Cancer Center in Houston, and colleagues assessed the expression of 193 total and phosphoproteins in 34 SCLC and 74 NSCLC cell lines to examine the molecular differences which contribute to the distinct clinical behavior of these tumors.
The researchers found that SCLCs had significantly increased levels of E2F1-regulated factors, including enhancer of zeste homolog 2 (EZH2), thymidylate synthase, apoptosis mediators, and DNA repair proteins. SCLCs also exhibited lower levels of several receptor tyrosine kinases and reduced activation of phophoinositide 3-kinase and Ras/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) pathways. In SCLCs, the DNA repair protein and E2F1 co-activator, PARP1, was highly expressed at the mRNA and protein level. PARP1 and EZH2 knockdown inhibited SCLC growth. Compared with NSCLCs, SCLCs were significantly more sensitive to PARP inhibitors, with PARP inhibition downregulating key components of DNA repair machinery.
"Our data reveal fundamental differences in the patterns of pathway activation in SCLCs and NSCLCs and identify several potential therapeutic targets for SCLCs, including PARP1 and EZH2," the authors write. "On the basis of these results, clinical studies evaluating PARP and EZH2 inhibition, together with chemotherapy or other agents, warrant further investigation."
Several authors disclosed financial ties to the pharmaceutical industry.