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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Ovarian cancer: targeting the untargetable
1From the Harvard Medical School, Massachusetts General Hospital, Boston, MA.
Abstract:
The premise that all tumors are targetable has been met with some controversy in the approach to epithelial ovarian cancer (EOC). Genomic analysis shows that these tumors (specifically, high-grade serous carcinomas) are genomically unstable and lack actionable driver mutations, much like HER2 in breast and gastric cancers. In this paper, Michael Birrer, MD, PhD, Massachusetts General Hospital, argues that the interpretation of genomic data in ovarian cancer requires a more thoughtful approach that necessitates a closer inspection of the data beyond the mere presence or absence of mutations. We must look at the extensive genomic alterations in DNA and, to understand more about the role of those genes affected by these changes, look beyond the tumor to the role of the stroma. As such, Dr. Birrer is arguing for the importance of translational research. This will be the key to precision medicine in ovarian cancer, as we approach drug discovery and improvements in treatment. Dr. Birrer is a world-renowned scientist who has devoted his career to the study of gynecologic cancers. He has published over 200 papers and written over 27 book chapters and reviews, served on numerous leadership positions in gynecologic oncology (including as co-chair of the National Cancer Institute's Gynecologic Cancer Steering Committee), and remains a clinician-scientist with an active lab and an active clinic. His career trajectory has shown me it is possible to be engaged as a researcher and a clinician and the work he has done has already impacted the care of patients with ovarian cancer. Don S. Dizon, MD, ASCO Educational Book Editor.
Insights
Epithelial ovarian cancer (EOC) presents genomic instability, challenging the idea of targetable tumors. A deeper analysis of genomic alterations and stromal factors is crucial for advancing precision medicine and drug discovery in EOC.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Epithelial ovarian cancer (EOC) is characterized by genomic instability.
- High-grade serous carcinomas often lack actionable driver mutations, complicating targeted therapy approaches.
- The premise of universally targetable tumors faces controversy in EOC management.
Purpose of the Study:
- To advocate for a nuanced interpretation of genomic data in ovarian cancer.
- To emphasize the importance of examining extensive genomic alterations beyond simple mutations.
- To highlight the role of stromal factors in EOC pathogenesis and treatment.
Main Methods:
- Review and interpretation of existing genomic data in epithelial ovarian cancer.
- Consideration of DNA alterations and their impact on gene function.
- Inclusion of the tumor microenvironment, specifically the stroma, in analysis.
Main Results:
- Genomic analysis reveals significant instability in EOC, particularly high-grade serous carcinomas.
- Ovarian tumors frequently lack straightforward, actionable mutations comparable to HER2 in other cancers.
- A comprehensive approach integrating tumor genomics and stromal interactions is necessary.
Conclusions:
- Precision medicine in ovarian cancer requires a deeper look at genomic data, including extensive alterations and stromal contributions.
- Translational research is essential for improving drug discovery and treatment strategies for EOC.
- Rethinking the interpretation of genomic data is key to advancing ovarian cancer care.
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