Ovarian, Uterine, and Cervical Cancers

Current Projects
Edmond M. Chan, MD

Defects in the cellular DNA repair machinery can promote cancer formation and cause cancer cells to rely on back-up DNA repair processes. These cancer cells are particularly vulnerable to drugs called PARP inhibitors, which target a DNA repair process known as homologous recombination. Dr. Chan hypothesizes that a similar treatment strategy can be used for cancers with deficiencies in DNA mismatch repair, which causes microsatellite—short, repeated sequences of DNA—instability (MSI). Microsatellite instability is found most often in certain colon, stomach, uterine and ovarian cancers. Using CRISPR screening technology, Dr. Chan discovered that cancer cells with faulty mismatch repair become dependent on a gene called WRN to survive. He is characterizing this vulnerability for MSI cancers with the goal of finding new drugs that inhibit this pathway.

Project title: "Validating a novel synthetic lethal target for microsatellite unstable cancers"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Adam J. Bass, MD
Cancer Type: Gastric, Gynecological, Colorectal
Research Area: Cancer Genetics
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
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