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Targeting Minimal Residual Disease in Ovarian Cancer

TARGETING MINIMAL RESIDUAL DISEASE IN OVARIAN CANCER

The majority of patients with ovarian cancer are diagnosed with late-stage disease. These women face cure rates as low as 15% depending on the subtype of ovarian cancer, a statistic that has not changed over the past several decades.

The majority of patients with ovarian cancer are diagnosed with late-stage disease. These women face cure rates as low as 15% depending on the subtype of ovarian cancer, a statistic that has not changed over the past several decades.

PROJECT HIGHLIGHTS

  • A key factor underlying these poor cure rates is the ability of cancer cells resistant to chemotherapy to persist after frontline treatment.
  • This persistent minimal residual disease (MRD) is clinically undetectable and represents “the seed” that eventually manifests as cancer recurrence.
  • The goal of this project is to transform the care of women with ovarian cancer by developing unprecedented capabilities for understanding and targeting MRD.
  • To do this, the team will develop and benchmark the accuracy of new blood biopsy and “second-look” surgical technologies to monitor this state at high resolution including extensive use of single-cell analysis.
  • Currently, trials of investigational frontline therapies use progression free survival as their primary endpoint. Significant costs and long duration of these trials stifle innovation and development of more effective initial therapies. This project includes clinical trials to use the rate of MRD after frontline therapy as a primary endpoint, de-risking testing of novel frontline therapies.

MEET THE TEAM

AllDana-Farber Cancer InstituteMIT’s Koch Institute for Integrative Cancer ResearchThe University of Texas MD Anderson Cancer CenterThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsMemorial Sloan Kettering Cancer Center

MEET THE TEAM

View Team
AllDana-Farber Cancer InstituteMIT’s Koch Institute for Integrative Cancer ResearchThe University of Texas MD Anderson Cancer CenterThe Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsMemorial Sloan Kettering Cancer Center

PROJECT SUMMARY

A key factor underlying poor ovarian cancer cure rates is the ability of cancer cells resistant to chemotherapy to persist after frontline therapy. This persistent minimal residual disease (MRD) is clinically undetectable and represents “the seed” that eventually manifests as cancer recurrence. Over the last four decades, the main approach to slow the recurrence of ovarian cancer has been to place patients on one-size-fits-all “maintenance” therapies, as opposed to focusing specifically on unique vulnerabilities of the remaining cancer cells. Developing more effective therapies requires overcoming critical knowledge gaps regarding the biology of MRD.

The goal of this project is to transform the care of women with ovarian cancer by developing unprecedented capabilities for understanding and targeting MRD. Specifically, the team will take two complementary approaches. First, they will examine the limits of detection of blood-biopsy approaches to detect minute levels of residual cancer DNA in the blood after surgery is complete. Second, they will leverage “second-look laparoscopies,” surgical procedures in which latent MRD cells can be harvested and subjected to single-cell and spatial analysis to probe their evolutionary trajectories and states. These investigations will also be used to uncover novel immune and targeted therapies specific to the MRD phase of ovarian cancer. These putative targets will be tested and prioritized in mouse models, incorporating the use of novel therapeutic approaches such as nanoparticle delivery.

The multi-institutional team will also have a major clinical component. The team will partner with several drug companies developing new therapeutics, such as CDK and PARP inhibitors, which are thought to be efficacious in ovarian cancer patient populations with tumors harboring specific molecular features. Rather than performing these clinical studies with standard clinical endpoints, the team intends to treat and use MRD analyses to also determine efficacy. This approach aims to develop MRD as a “surrogate endpoint” for the accelerated evaluation of ovarian cancer drugs. If successful, this approach could have major implications for speeding up drug approval in this devastating disease. Finally, the team will also grow and treat organoid cultures in the laboratory from these clinical investigations. These three-dimensional laboratory cultures may hold potential to predict which patients will and will not respond, and this project aims to further demonstrate the power of this emerging technological approach for this disease.

Pursuing these questions in the setting of a single, multi-disciplinary Break Through Cancer team-based effort creates a fertile ecosystem for nurturing new ideas and new technologies to rapidly move laboratory insights to clinical trials.

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Break Through Cancer was created in February 2021 with an extraordinary matching gift of $250,000,000. Every gift to the Foundation supports groundbreaking cancer research and helps us to meet our matching commitment.

For questions about giving please email Lisa Schwarz, Chief Philanthropy Officer at LMS@BreakThroughCancer.org

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