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Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer
- Source :
- BMC Cancer, BMC Cancer, Vol 20, Iss 1, Pp 1-10 (2020)
- Publication Year :
- 2020
- Publisher :
- BioMed Central, 2020.
-
Abstract
- Background 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. Methods 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. Results 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. Conclusions 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 :
- 0301 basic medicine
Oncology
Male
Cancer Research
Patient derived xenograft
Colorectal cancer
DNA Mutational Analysis
Druggability
chemistry.chemical_compound
Mice
0302 clinical medicine
Surgical oncology
Medicine
Receptors, Platelet-Derived Growth Factor
RNA-Seq
Precision Medicine
biology
Metastatic colorectal cancer
Ponatinib
Standard of Care
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
src-Family Kinases
Fibroblast growth factor receptor
030220 oncology & carcinogenesis
Female
Colorectal Neoplasms
Platelet-derived growth factor receptor
Research Article
Signal Transduction
medicine.medical_specialty
Antineoplastic Agents
lcsh:RC254-282
03 medical and health sciences
Internal medicine
Cell Line, Tumor
Genetics
Animals
Humans
business.industry
Cancer
Precision medicine
medicine.disease
High-throughput drug screen
Receptors, Fibroblast Growth Factor
Xenograft Model Antitumor Assays
High-Throughput Screening Assays
030104 developmental biology
Receptors, Vascular Endothelial Growth Factor
chemistry
Mutation
biology.protein
Drug Screening Assays, Antitumor
business
Subjects
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....6151a9fbab18e836b3f6074ad4af93eb