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- Title
Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer.
- Authors
Altunel, Erdem; Roghani, Roham S.; Chen, Kai-Yuan; Kim, So Young; McCall, Shannon; Ware, Kathryn E.; Shen, Xiling; Somarelli, Jason A.; Hsu, David S.
- Abstract
<bold>Background: </bold>Metastatic colorectal cancer (CRC) continues to be a major health problem, and current treatments are primarily for disease control and palliation of symptoms. In this study, we developed a precision medicine strategy to discover novel therapeutics for patients with CRC.<bold>Methods: </bold>Six matched low-passage cell lines and patient-derived xenografts (PDX) were established from CRC patients undergoing resection of their cancer. High-throughput drug screens using a 119 FDA-approved oncology drug library were performed on these cell lines, which were then validated in vivo in matched PDXs. RNA-Seq analysis was then performed to identify predictors of response.<bold>Results: </bold>Our study revealed marked differences in response to standard-of-care agents across patients and pinpointed druggable pathways to treat CRC. Among these pathways co-targeting of fibroblast growth factor receptor (FGFR), SRC, platelet derived growth factor receptor (PDGFR), or vascular endothelial growth factor receptor (VEGFR) signaling was found to be an effective strategy. Molecular analyses revealed potential predictors of response to these druggable pathways.<bold>Conclusions: </bold>Our data suggests that the use of matched low-passage cell lines and PDXs is a promising strategy to identify new therapies and pathways to treat metastatic CRC.
- Subjects
UNITED States. Food &; Drug Administration; VASCULAR endothelial growth factor receptors; FIBROBLAST growth factor receptors; PLATELET-derived growth factor; COLORECTAL cancer; INDIVIDUALIZED medicine
- Publication
BMC Cancer, 2020, Vol 20, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-020-07090-y