In vivo functional screens reveal

Authors: Lauren Brumage, Scott Best, Daniel S. Hippe, Eli Grunblatt, Pritha Chanana, Feinan Wu, Myung Chang Lee, Zhe Ying, Ali Ibrahim, Jae Heun Chung, Anna Vigil, Jackson Fatherree, Slobodan Beronja, Patrick Paddison, Lucas Sullivan, Barzin Nabet, David MacPherson

Published: 2025-04-23

DOI: 10.1126/sciadv.adq7084

Source: Full article


Abstract

Exquisitely chemosensitive initially, small cell lung cancer (SCLC) exhibits dismal outcomes owing to rapid transition to chemoresistance. Elucidating the genetic underpinnings has been challenging owing to limitations with cellular models. As SCLC patient-derived xenograft (PDX) models mimic therapeutic responses, we perform genetic screens in chemosensitive PDX models to identify drivers of chemoresistance. cDNA overexpression screens identify