April 25, 2022

Molecular testing across tumor types

The KRAS inhibitor sotorasib is newly approved for one kind of lung cancer; Vanderbilt researchers ask if it should be considered for another type if the tumor has the gene mutation it targets.

KRAS gene mutations — found in about 25% of tumors — are drivers of lung, colorectal and pancreatic cancers. 

KRAS had long been considered an “undruggable” target because of its structure, but the first KRAS-blocking drug, sotorasib, was approved in 2021 as second-line or later therapy in non-small cell lung cancer (NSCLC) patients with a certain KRAS mutation (G12C). 

Wade Iams, MD, and colleagues pose the question of using sotorasib for a patient with a spontaneous G12C KRAS mutation in a different cancer, small cell lung cancer (SCLC). It is the second reported case of a G12C mutation in SCLC, they note in JTO Clinical and Research Reports. 

The patient responded well to first-line therapy, but will present a unique challenge at progression, and the authors question if the patient would benefit from sotorasib. They also suggest that finding such genetic alterations in other tumors may argue for expanded molecular testing across tumor types as the number of approved targeted therapies increases.

Other study authors included Meridith Balbach and Rosana Eisenberg, MD. The research was supported by a National Comprehensive Cancer Network Young Investigator Award to Iams.