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We have generated a panel of 66 patient-derived xenograft models (PDXs) of SCLC from biopsy specimens and circulating tumor cells (CTCs). These models stably maintain somatic genomic alterations from patients, and faithfully mirror their responses to DNA damaging therapies. The strongest correlate with sensitivity to both regimens was basal expression of interferon-stimulated genes (ISG’s), and cross-resistance was marked by low basal ISG expression. This result was surprising, as xenografts were grown and tested in severely immunocompromised mice. Investigation of the ISG signature presents a novel opportunity to dissect the molecular underpinnings of cross-resistance, a problem that has beleaguered management of SCLC for over three decades.
Video Overview: https://youtu.be/f43UylQ1xdc
Benjamin Drapkin, MD, PhD
MGH Cancer Center
STO gratefully acknowledges educational grants in partial support of this activity from:
Novartis Pharmaceuticals Corp.