Molecular subgroups of non-small cell lung cancer predict tumor behavior, reveal treatment targets

A recent study, published in the journal Oncotarget, describes further scientific insight into the metastatic patters of Epidermal Growth Factor Receptor (EGFR) mutated NSCLCs. The authors determined that bio-molecular characteristics and genotype may influence the metastatic process in NSCLC tumors, and might help the development of enrichment strategies for tumor genotyping in these tumors, especially in the presence of limited tissue availability. Furthermore, the understanding that EGFR-mutated NSCLCs metastasize more frequently in certain sites might help clinicians for a more appropriate selection of patients for EGFR mutational testing beyond current clinical parameters, such as tumor histotype, ethnicity or smoking status.

The study includes work done by Prof. Vincenzo Adamo, of the University of Messina, Italy, in collaboration with Prof. Antonio Giordano, Director of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia, as well as other colleagues at the University of Siena, Italy

Exploring the link between oncogene status and metastatic behavior in non-squamous NSCLCs, the authors analyzed the different metastatic patterns, at baseline and during the course of the disease in a cohort of 137 Caucasian patients.

They reported unique metastatic distributions between EGFR-mutated and EGFR wild type non-squamous NSCLCs, since EGFR mutated NSCLCs tended to develop at baseline with a higher frequency compared with wild type tumors, brain metastases, lung metastases, pleural involvement, and bone metastases. However, the presence of EGFR mutations is associated with a longer median overall survival (almost double) compared with those without EGFR mutations when treated with specific targeted agents. Moreover, the EGFR mutational status was a predictor of longer overall survival also in the presence of brain metastases, a clinical condition commonly associated with a dismal prognosis.

"In order to move this research into clinical applications for EGFR-mutated NSCLCs, we hope to address the growing list of molecular tests required for an adequate treatment of such patients," says Dr. Adamo. "The most pressing challenge is limited tumor tissue availability, due to the disease being commonly diagnosed through small tumor biopsies or cytological samples, given its peculiar localization. Therefore, strategies for the optimal selection of patients for molecular testing are eagerly awaited," Adamo concluded.