Related Experiment Video
Updated: Dec 13, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
A Proof of Concept for Biomarker-Guided Targeted Therapy against Ovarian Cancer Based on Patient-Derived Tumor
Adam C Palmer1,2, Deborah Plana1,3,4, Hui Gao5
1Laboratory of Systems Pharmacology, Harvard Medical School, Boston, Massachusetts.
Abstract:
Advanced ovarian cancers are a leading cause of cancer-related death in women and are currently treated with surgery and chemotherapy. This standard of care is often temporarily successful but exhibits a high rate of relapse, after which, treatment options are few. Here we investigate whether biomarker-guided use of multiple targeted therapies, including small molecules and antibody-drug conjugates, is a viable alternative. A panel of patient-derived ovarian cancer xenografts (PDX), similar in genetics and chemotherapy responsiveness to human tumors, was exposed to 21 monotherapies and combination therapies. Three monotherapies and one combination were found to be active in different subsets of PDX. Analysis of gene expression data identified biomarkers associated with responsiveness to each of the three targeted therapies, none of which directly inhibits an oncogenic driver. While no single treatment had as high a response rate as chemotherapy, nearly 90% of PDXs were eligible for and responded to at least one biomarker-guided treatment, including tumors resistant to standard chemotherapy. The distribution of biomarker positivity in The Cancer Genome Atlas data suggests the potential for a similar precision approach in human patients. SIGNIFICANCE: This study exploits a panel of patient-derived xenografts to demonstrate that most ovarian tumors can be matched to effective biomarker-guided treatments.
Insights
Biomarker-guided targeted therapies offer new hope for advanced ovarian cancer patients. This approach successfully treated nearly 90% of patient-derived tumors, including those resistant to chemotherapy.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Advanced ovarian cancer is a leading cause of cancer-related death in women.
- Current treatments (surgery and chemotherapy) often lead to relapse with limited options.
- Investigating targeted therapies as an alternative to standard care is crucial.
Purpose of the Study:
- To evaluate the efficacy of biomarker-guided targeted therapies in advanced ovarian cancer.
- To identify biomarkers predictive of treatment response.
- To assess the potential for a precision medicine approach in ovarian cancer.
Main Methods:
- Utilized a panel of patient-derived ovarian cancer xenografts (PDX) mirroring human tumor characteristics.
- Exposed PDX models to 21 monotherapies and combination targeted therapies.
- Analyzed gene expression data to identify biomarkers associated with treatment responsiveness.
Main Results:
- Three monotherapies and one combination therapy demonstrated activity in distinct PDX subsets.
- Biomarkers for responsiveness to targeted therapies were identified, independent of direct oncogenic driver inhibition.
- Nearly 90% of PDX models responded to at least one biomarker-guided treatment, including chemotherapy-resistant tumors.
Conclusions:
- Biomarker-guided targeted therapies represent a promising strategy for advanced ovarian cancer.
- This precision approach can effectively treat a majority of ovarian tumors, including resistant types.
- Findings suggest potential for similar biomarker-guided treatment strategies in human patients.
