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Molecular profiling and commercial predication assays in ovarian cancer: still not ready for prime time?
1From the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD.
Abstract:
Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach-rather than undergoing rigorous scientific examination-is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.
Insights
Matching ovarian cancer treatments to individual patients remains a challenge. Current chemoresponse assays and molecular profiling lack sufficient evidence for routine clinical use, though they aid research.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Accurate ovarian cancer diagnosis and personalized treatment selection are critical for improving patient outcomes.
- In vitro chemoresponse assays have been used for decades but lack level one evidence for clinical application.
- Emerging molecular profiling assays offer insights but require rigorous scientific validation.
Purpose of the Study:
- To evaluate the current status and readiness of chemoresponse assays and molecular profiling for clinical use in ovarian cancer.
- To discuss the role of molecular patterns in improving ovarian cancer diagnosis and guiding therapy.
- To assess the predictive value of genetic mutations, such as BRCA1/2, for targeted therapies.
Main Methods:
- Review of existing literature and clinical experience with in vitro chemoresponse testing.
- Analysis of the contribution of molecular profiling to understanding ovarian cancer subtypes.
- Examination of the evidence supporting the use of specific molecular markers (e.g., BRCA mutations) for treatment selection.
Main Results:
- Neither chemoresponse assays nor molecular profiling have demonstrated sufficient clinical utility or evidence for routine application in ovarian cancer treatment.
- Molecular profiling has advanced the understanding of ovarian cancer biology and subtype-specific patterns.
- BRCA1/2 mutations show predictive value for poly(ADP-ribose) polymerase inhibitor response, but few other druggable targets have been identified.
Conclusions:
- Chemoresponse assays and molecular profiling are not yet ready for widespread clinical adoption in ovarian cancer management.
- Continued use as research tools is encouraged, with a strong emphasis on clinical trial validation.
- Further research is needed to identify reliable molecular targets and validate predictive biomarkers for personalized ovarian cancer therapy.
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