Photo Credit: MicrovOne

Squamous cell cancer (SqCC) of the lung has limited targeted therapy options, making molecular characterization through next-generation sequencing (NGS) beneficial for identifying potential targets. In the Lung-MAP SWOG S1400 trial, Mary Redman, PhD, and colleagues analyzed NGS data from 1,672 patients with stage 4 or recurrent SqCC, sequencing 313 cancer-related genes. The study, which was published in the Journal of Thoracic Oncology, identified mutually exclusive gene alterations. Key findings included two distinct sets of mutually exclusive alterations: NFE2L2, KEAP1, and PARP4, as well as CDKN2A and RB1. PARP4 had frequent mutations indicating functional significance, and NFE2L2 and KEAP1 alterations were linked to poorer survival. “As the largest dataset to-date of lung SqCC profiled on a clinical trial, the S1400 NGS dataset establishes a rich resource for biomarker discovery,” Dr. Redman and colleagues wrote. “Mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations suggests that PARP4 may have an uncharacterized role in a key pathway known to impact oxidative stress response and treatment resistance.”