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Senthil Muthuswamy, PhD
Director, Program in Cell Biology,
Beth Israel Deaconess Medical Centre,
Associate Professor, Department of Medicine,
Harvard Medical School
- Seeking to advance vaccine development and targeted treatments in early and advanced breast cancer.
- Laboratory studies are conducted to explore novel therapeutic strategies and vaccine development to improve the treatment and prevention of metastasis.
- These studies may lead to advancements to benefit patients with advanced breast cancer and those at high risk of developing invasive breast cancer.
Estrogen receptor (ER)-positive breast cancer is the most commonly diagnosed breast cancer. It is treatable with anti-estrogen therapies, but resistance to these therapies can lead to advanced breast cancer. Dr. Muthuswamy has identified a therapeutic target to prevent drug resistance. He is testing this as well as a breast cancer vaccine in laboratory studies.
Full Research Summary
Resistance to anti-estrogen (endocrine) therapies is a persistent clinical challenge, and new treatments are urgently needed to prevent estrogen receptor-positive tumors from progressing and spreading to other tissues.
Dr. Muthuswamy is pursuing groundbreaking research in two separate, but related studies that may provide new treatment and prevention options.
In one study, his team is following up on their observation that estrogen-receptor (ER)- positive cells can proliferate well in limited nutrient conditions, such as those present at tumor sites, by upregulating a nutrient transporter called SLC7A5. Cells resistant to tamoxifen have high levels of SLC7A5, and inhibiting SLC7A5 makes the cells sensitive to tamoxifen again, suggesting that SLC7A5 is a new target for endocrine resistance.
The team will validate this observation using innovative methods to generate new endocrine resistant models of breast cancer. If laboratory studies are successful, they will initiate a clinical trial to inhibit SLC7A5 in patients with metastatic ER-positive disease.
The second study involves testing a vaccination strategy in laboratory models, which if successful, will move to the first-in-human studies for patients with breast cancer.
Dr. Muthuswamy believes his team can develop effective breast cancer vaccines for both advanced cancers and for pre-malignant disease to prevent progression. These two complimentary approaches may benefit patients with metastatic disease and prevent cancer development in patients with high-risk premalignant disease.
Senthil K. Muthuswamy, Ph.D., is the Director of the Cell Biology Program at the Cancer Centre at Beth Israel Deaconess Medical Centre, Harvard Medical School. Dr. Muthuswamy received his Ph.D. from McMaster University, Canada and did his postdoctoral fellowship with Joan Brugge at Harvard Medical School. He began his independent faculty position at Cold Spring Harbor Laboratory, New York and subsequently moved to Princess Margaret Cancer Centre as the Margaret Lau Chair in Breast Cancer Research. In 2015, he moved to BIDMC to direct the Cell Biology program at the Cancer Center at BIDMC. Dr. Muthuswamy is a recipient of Rita Allen Scholar award, V Foundation scholar award, US Army Era of Hope Scholar Award, and the Canadian Society of Biochemistry and Molecular & Cellular Biology young scientist award for outstanding research achievements.
His laboratory pioneered both the development and use of three-dimensional culture methods for modeling carcinoma of breast and pancreas and understanding the unexplored role played by cell polarity proteins in regulating the biology of cancer. He was the first to identify cell polarity proteins, such as PARD6, PARD3 and SCRIB, as critical regulators of cell death, cell proliferation and metastasis either by themselves or in cooperation with oncogenes, such as ERBB2 and MYC, in breast cancer. His group continues to investigate and discover how cell polarity proteins regulate cell biology of cancer and normal cells and its impact on stress adaptation and therapy resistance.
He recently launched a new initiative in his lab to bridge cancer biology and clinical cancer care, called “Microscope to Stethoscope”. His team is developing and implementing personalized tumor organoid culture platforms to assist patients and oncologists by performing a lab-based screen of available treatment options to identify the best possible cancer treatment for each patient. This effort is married to his long-standing interest in using patient-derived tumor models for translational and discovery research to find better cancer treatments.