Abstract IA05: Circulating tumor cells in lung cancer: Biomarkers, biology, and mouse models to study drug resistance

Abstract

Abstract SCLC patients (∼75%) respond well initially to standard chemotherapy (platinum/etoposide) but drug resistant disease relapse ensues rapidly. Most Small Cell Lung Cancer (SCLC) patients present with metastases, consequently tumor resection is rare and tumor biopsy is rarely obtained at disease relapse to explore drug resistance mechanisms. Targeted therapies have yet to impact SCLC patient outcomes, new drug targets and biomarkers measured in minimally invasive samples are required. Using EpCam dependent CellSearch technology, we showed that CTCs are prevalent in SCLC and CTC number is an independent prognosticator. SCLC CTC number is pharamcodynamic and CTCs are amenable to biomarker assay development (protein expression, omic profiling, FISH etc.) to be applied in clinical trials. We also developed unique patient CTC derived mouse models (CDX) to study SCLC biology, search for new drug targets, develop biomarkers and explore drug resistance mechanisms. Successful CDX engraftment has been observed so far in ∼45% cases. The molecular landscape of CDX can be compared to that of single, isolated CTCs from the same patient. CDX are readily passaged and their response to cisplatin/etoposide closely mimics the donor patient. CDX offer unparalleled opportunity to interrogate drug resistance mechanisms as paired models can be generated at presentation (chemosensitive) and again at relapse (drug resistance). Our data demonstrate that serial blood sampling with CDX and CTC molecular analysis could facilitate delivery of precision medicine to improve outcomes in SCLC. A program of evaluation of novel therapeutics in CDX models, the development of orthotopic CDX SCLC and NSCLC CDX are underway. Citation Format: Caroline Dive, Chris Morrow, Ged Brady, Fiona Blackhall. Circulating tumor cells in lung cancer: Biomarkers, biology, and mouse models to study drug resistance. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr IA05.