Shreoshi Pal Choudhuri, Luc Girard, Jun Yi Stanley Lim, Jillian F Wise, Braeden Freitas, Di Yang, Edmond Wong, Seth Hamilton, Victor D Chien, Yoon Jung Kim, Collin Gilbreath, Jun Zhong, Sarah Phat, David T Myers, Camilla L Christensen, Hanieh Mazloom-Farsibaf, Marcello Stanzione, Kwok-Kin Wong, Yin P Hung, Anna F Farago, Catherine B Meador, Nicholas J Dyson, Michael S Lawrence, Sihan Wu, Benjamin J Drapkin
Small cell lung cancer (SCLC) presents as a highly chemosensitive malignancy but acquires cross-resistance after relapse. This transformation is nearly inevitable in patients but has been difficult to capture in laboratory models. Here, we present a pre-clinical system that recapitulates acquired cross-resistance, developed from 51 patient-derived xenograft (PDX) models. Each model was tested in vivo against three clinical regimens: cisplatin plus etoposide, olaparib plus temozolomide, and topotecan. These drug-response profiles captured hallmark clinical features of SCLC, such as the emergence of treatment-refractory disease after early relapse...
February 22, 2024: Cancer Discovery