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Joseph R. Bertino, MD
Professor of Medicine & Pharmacology
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey
Goal: To identify new therapeutic targets for the treatment of breast cancer, particularly BRCA-driven triple-negative breast cancer (TNBC).
Impact: Dr. Bertino is testing a new antibody-drug conjugate that has been shown to shrink BRCA-driven TNBC tumors in laboratory studies. If proven effective in clinical trials, the drug could potentially be used alone or with other therapies to treat patients with this aggressive form of breast cancer.
What’s next: The team is testing a second generation of the drug – one that is attached to a novel toxin, and may be even more effective. They plan to test it alone and in combination with other therapies currently approved for treatment of BRCA-driven-TNBC, including drugs that block DNA repair and immunotherapy drugs.
There are limited targeted therapies for TNBC, and those that have been approved are not equally effective for all patients. Chemotherapy remains the standard of care for most of these patients, so new therapies are urgently needed. Dr. Bertino has developed a promising novel treatment for TNBC resulting from mutations in the BRCA gene. His studies have shown that the drug reduces tumors in laboratory models of the disease. He is now testing a conjugated version of the drug that may be even more effective.
Full Research Summary
Research area: Investigating novel antibody drug conjugates as more effective therapies for triple-negative breast cancer (TNBC) caused by mutations in the BRCA genes.
Impact: TNBC is difficult to treat because it lacks the three most common targets for breast cancer treatment (estrogen, progesterone, and HER2). Because TNBC has a poor prognosis, more effective treatments are urgently needed. Dr. Bertino is pursuing new therapeutic targets in order to develop effective treatment options with minimal toxicity for patients with TNBC.
Current investigation: He and his team have been working on a novel treatment that uses an antibody that binds to an enzyme (matriptase) found on TNBC cells.
What he’s learned so far: Matripase is a membrane bound protein found on BRCA-driven TNBC cells and is known to play role in tumor initiation, progression, and metastasis. Dr. Bertino’s team have developed an antibody-drug conjugate drug that binds to matriptase on TNBC cell and then delivers a toxic drug that kills the cells. In their laboratory studies, they have shown that a matriptase-ADC shrank TNBC tumors and had no side effects presumably because it does not significantly bind to normal cells.
What’s next: Dr. Bertino and his colleagues will build on their findings and test a second generation matriptase-ADC which has a novel toxin attached, one that causes tumor DNA damage. This novel matripstase-ADC has the potential to be even more effective in treating TNBC than the first generation ADC. They will test it alone and in combination with an inhibitor of DNA repair. The results of these studies will determine the best ADC for future development and translation into the clinic.
Dr. Joseph R. Bertino attended Cornell University and Downstate Medical School, SUNY. After internship and residency, he was a Fellow in Hematology and Biochemistry at The University of Washington. In 1961, he joined the faculty at Yale in Pharmacology/Medicine where he held several positions, including the first Director of Yale Cancer Center in 1973. He relinquished this position when he was awarded an ACS research professorship in 1975. He left Yale in 1987 for Memorial Sloan Kettering Cancer Center, where he was Head of the Molecular Pharmacology and Clinical Investigation Program. In 2002, he joined the Rutgers Cancer Institute of New Jersey as their Chief Scientific Officer and a University Professor of Medicine & Pharmacology at the Rutgers Robert Wood Johnson Medical School.
Dr. Bertino has received many honors for his work. He is a past president of AACR and ASCO, and was founding editor of the JCO. He continues to develop novel and treatments for cancer. He recently discovered a peptide that can regress E2F-1 oncogene addicted tumors, and is developing novel antibody-toxin conjugates to treat breast cancer.
BCRF Investigator Since
The Ulta Beauty Award