Past Research has been Limited
Carcinosarcoma represents 1-2% of ovarian cancers and 3-4% of uterine cancers and is extremely aggressive. As a leading cancer center, Massachusetts General Hospital (MGH) Cancer Center sees a disproportionately higher number of women with GCS due to its exceptional care and research programs. At present, 10% of Dr. Michael Birrer’s patients have GCS.
The research on this tumor has been limited. The cancer genome atlas (TCGA) only analyzed high-grade serous ovarian cancers. Dr. Birrer believes the molecular biology of GCS is likely to be completely different from the more common high-grade serous cancers. This may explain the more aggressive nature and chemo-resistance of GCS. Molecular characterization of GCS tumors will open new avenues in research and treatment for this disease.
Scope of the Current Research
Here is a summary of the initial focus of The GCS Project. It is very scientific, and I have provided references in an attempt to simplify the information.
- Determine the full genetic landscape of carcinosarcoma C/S of the ovary and the uterus.
- Perform whole-exome sequencing or DNA analysis of tumor by the Broad Institute. For a detailed explanation, visit these sites:
- Map mutations within the tumor to determine the heterogeneity of C/S tumors. For a better understanding of heterogeneity, visit these sites:
- Mutation identification will lead to identification of ACTIONABLE MOLECULAR EVENTS.
- Determine the transcriptome (RNA) of the tumors that will lead to the identification of important biologic/biochemical pathways . What does this mean? Visit these references:
- Identification of these pathways will lead to the development of novel therapeutic approaches to C/S.
- Discover the molecular basis for metastasis.
- Using tissue samples collected from biopsies separated both anatomically and over time will be analyzed to provide a unique genomic view the molecular basis for metastasis and the evolution of the tumor over time to understand the evolutionary patterns accompanying the metastatic process and identify potential drivers of metastasis.
The Research Has Begun …
The Gynecologic Carcinosarcoma (GCS) Research Project at the MGH Cancer Center is rapidly moving forward. Led by Dr. Birrer, the research team has:
- Identified and characterized 25 GCS samples with both primary tumor and matching metastasis sites — including mine.
- Conducted high through-put sequencing on these tumor samples and will compare the genetic mutations in the primary tumor to those of the metastatic site. This data will allow for the identification of important pathways that enable the tumor to grow and progress. This information will ultimately help the team identify potential targets for treatment.
Dr. Birrer and his team are testing these tumor samples for immune infiltrates.
- Many tumors are recognized as foreign by our immune system, and yet the immune cells are tricked into not attacking the tumor cells.
- By identifying the quantity and type of immune cells which are present within these GCS tumors, the research team anticipates that they will be able to identify patients who could benefit from emerging therapeutic agents designed to boost the immune system to kill cancer cells.