Sheheryar Kabraji, BMBCh
Physician, Medical Oncology
Dana-Farber Cancer Institute
American Association for Cancer Research
Goal: To prevent recurrence in patients with HER2-positive breast cancer.
Impact: Though effective HER2-targeting drugs have greatly improved outcomes for patients with HER2-positive breast cancer, relapse and recurrence still occur because some cancer cells develop drug resistance and survive. Dr. Kabraji is working to understand what drives tumor recurrence how to prevent it.
What’s next: Dr. Kabraji and his team will use a model of HER2-positive breast cancer to target residual cancer cells that cause recurrence and stimulate an anti-tumor immune response to kill them.
Treatment of HER2-positive breast cancer has improved greatly, but drug resistance can occur, leading to disease recurrence. Dr. Kabraji aims to elucidate the molecular environment of surviving cancer cells and what triggers them to grow into tumors. He hopes to develop therapies that stimulate an anti-tumor immune response to kill surviving cancer cells and prevent recurrence.
Research area: Preventing relapse and recurrence in patients with HER2-positive breast cancer.
Impact: The treatment of HER2-positive breast cancer with targeted therapies has improved patient outcomes, but relapse and recurrence still occur. Tumors can shrink with effective therapy; however, some cancer cells develop drug resistance and survive, known as residual disease (RD). Dr. Kabraji’s American Association for Cancer Research work, supported by BCRF, is focused on targeting and eliminating RD after HER2-positive breast cancer treatment, which could ultimately lead to novel therapeutic strategies to prevent recurrence.
Current investigation: In earlier work, Dr. Kabraji has shown that RD is made up of “sleeping” quiescent cancer cells (QCCs) that dampen the anti-tumor immune response. He and his team aim to target these cells and stimulate an anti-tumor response to kill them. By studying a HER2-positive breast cancer model and tissues from patients treated with HER2-targeted therapy, Dr. Kabraji and his team will investigate the immune changes seen when tumors shrink to RD and aim uncover how QCCs suppress the anti-tumor response. They will also test a drug that targets QCCs combined with immunotherapy, which stimulates the anti-tumor immune response and may prevent tumors from recurring. Dr. Kabraji’s work will help identify patients at risk for RD and may ultimately lead to new treatments to prevent relapse and recurrence in patients with HER2-positive breast cancer.
Sheheryar Kabraji, BMBCh received his medical degree from Oxford University Medical School and completed internal medicine residency at Massachusetts General Hospital. As a medical oncology fellow in the Dana-Farber/Partners Hematology/Oncology Fellowship Program, he undertook postdoctoral research in the laboratory of Dr. Sridhar Ramaswamy at the Mass General Cancer Center where he demonstrated that AKTlow quiescent cancer cells can be found in residual breast tumors after neoadjuvant chemotherapy. Dr Kabraji is a breast medical oncologist at the Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, and Instructor in Medicine at Harvard Medical School. Dr Kabraji’s research in the Zhao Laboratory at Dana-Farber Cancer Institute focuses on cancer cell quiescence as a mechanism of tumor drug resistance in localized and metastatic breast cancer.
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