Ovarian, Uterine, and Cervical Cancers

Current Projects
Jonathan C. Dudley, MD

Earlier cancer detection usually means a greater chance of remission or cure, but cost-effective and highly specific cancer screening is not yet available for most cancers. More than 90 percent of cancers harbor aneuploidy, an abnormal number of chromosomes in a cell; this abnormality is highly specific for cancer and can be detected with DNA sequencing. Dr. Dudley is developing a new approach for detecting cells with abnormal amounts of DNA, which could identify cancer sooner. He aims to apply this approach to urine and Pap smear samples to create an inexpensive and sensitive screening test for bladder, ovarian and endometrial cancers.

Project title: "Earlier detection of cancer in body cavity fluids through aneuploidy analysis after cell enrichment and partitioning"
Institution: The Johns Hopkins University School of Medicine
Named Award: Gordon Family Physician-Scientist
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Bert Vogelstein, MD
Cancer Type: Gynecological, Kidney and Bladder
Research Area: Diagnostics
Christopher A. Klebanoff, MD

A form of cancer immunotherapy termed adoptive T cell transfer (ACT) can induce long-lasting remissions in patients with advanced blood cancers. In this approach, T white blood cells specific for proteins found on the surface of cancer cells (antigens) are activated and expanded outside the immunosuppressive environment of a cancer patient's body before re-infusion as a therapy. Thus far, this promising form of cancer immunotherapy has failed to work in most patients with cancers arising from solid organs, the leading cause of cancer-related deaths in adults. Two critical gaps in knowledge limit the ability of ACT to be successfully applied to solid cancers: 1) understanding which antigens on the surface of cancer cells can be targeted by T cells that do not have the potential to cross-react and injure normal tissues, and 2) insight into what factor(s) limit the ability of transferred T cells to expand and persist following re-infusion into a patient. Dr. Klebanoff seeks to use a genetic engineering approach to simultaneously address both these issues. Success of these efforts would be a decisive step forward toward extending the ability of ACT to deliver potentially curative responses in patients with common cancers, including those arising from the breast, uterus, cervix and colon.

Project title: "Clinical development of next-generation T cell receptor (TCR)-based adoptive immunotherapies for the treatment of patients with common epithelial malignancies"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Michel Sadelain, MD, PhD, and Larry Norton, MD
Cancer Type: Gynecological, Kidney and Bladder, Breast
Research Area: Immunotherapy
Kara L. McKinley, PhD

Dr. McKinley studies the lining of the uterus called the endometrium. The human endometrium is a uniquely powerful system to understand fundamental principles of regeneration, as it regenerates after menstruation approximately 400 times over the reproductive lifespan. Understanding this remarkable regenerative event is critical to combat the growing incidence of endometrial cancers, and to address the longstanding unmet needs of patients with endometriosis and adenomyosis. The McKinley laboratory studies the cellular and molecular mechanisms of endometrial regeneration, with a view to improving endometrial cancer screening and developing new fertility-preserving treatments.

Project title: "Physiology and pathology of the uterus"
Institution: Harvard University
Award Program: Dale Frey Scientist
Cancer Type: Gynecological, All Cancers
Research Area: Cell Biology
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