Pharmacogenomic signatures that predict drug response andresistance in high-grade serous ovarian cancer using patient-derived organoids and their exosomes
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2020
- Accession Number
- AD1104203
Entities
People
- Kelsi Andrade
Organizations
- University of Oklahoma Health Sciences Center