Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments.

Functional profiling of a cancer patient's tumor cells holds potential to tailor personalized cancer treatment. Here, we report the utility of fresh uncultured tumor-derived EpCAM+ epithelial cells (FUTCs) for ex vivo drug-response interrogation. Analysis of murine Kras mutant FUTCs demonstrates pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. By applying FUTC profiling on non-small-cell lung cancer patient samples, we report robust drug-response data in 19 of 20 cases, with cells exhibiting targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling is used to guide compassionate treatment. FUTC profiling identifies selective sensitivity to disulfiram and the combination of carboplatin plus etoposide, and the patient receives substantial clinical benefit from treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.

Geographic Variation in EGFR Mutation Frequency in Lung Adenocarcinoma May Be Explained by Interethnic Genetic Variation.

Our understanding of the etiology of EGFR-mutant lung cancer remains incomplete. One persistent finding in the literature is the geographic variation in the frequency of EGFR mutations in lung adenocarcinoma. We investigated the association between two biomarkers of East Asian ancestry, the genetic polymorphisms ectodysplasin A receptor gene (EDAR) V370A and ATP binding cassette subfamily C member 11 gene (ABCC11) G180A, and the frequency of EGFR mutations in patients with lung adenocarcinoma in a range of countries. The Pearson's linear correlation between the frequency of EGFR mutations and the EDAR polymorphism was 0.92 (p <2.2 × 10-10), and for the ABCC11 polymorphism it was 0.72 (p <1.6 × 10-4). These results suggest that the variation in the measured frequency of EGFR mutations in lung adenocarcinoma can be explained, at least in part, by interethnic genetic variation. To improve our understanding of this disease, studies exploring the genetic polymorphism(s) that cause these interethnic differences, as well as the mechanisms of actions through which they work, are warranted.