Pharmacogenomic signatures that predict drug response andresistance in high-grade serous ovarian cancer using patient-derived organoids and their exosomes
Technical Report,15 May 2019,14 May 2020
University of Oklahoma Health Sciences Center Oklahoma City United States
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High-grade serous ovarian carcinoma HGSC is the most common and lethal subtype of ovarian cancer due to the advanced stage at diagnosis and high rate of relapse with platinum resistance. Currently, individualized therapy is unattainable due to limited knowledge of early markers of drug resistance. Repetitive tumor sampling is an invasive approach and fails to account for tumor heterogeneity and the evolution of drug resistance. Better models for identifying patients that may develop chemotherapy resistance are required to make progress in treating patients with ovarian cancer. The hypothesis is that patient-derived organoids PDOs can be used to identify effective new therapies for HGSC and that analysis of responding and non-responding PDOs and their secreted exosomes can be used to identify markers that predict treatment response or resistance in patients. This will be addressed with the following aims Aim 1 will determine the sensitivity and resistance of HGSC PDOs to NCI-IND drugs as single agents and in combination with standard of care, Aim 2 will determine miRNA signatures that predict drug response from PDOs and their secreted exosomes, while Aim 3 will determine whether organoid response and drug response signatures from PDOs and their secreted exosomes correlate with actual patient response.
- Medicine and Medical Research