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Joshua Z. Drago, MD
Fellow, Medical Oncology
Memorial Sloan Kettering Cancer Center
New York, New York
Conquer Cancer, the ASCO Foundation
Goal: Developing a method to predict which breast cancer cells will be sensitive to treatment with antibody-drug conjugates.
Impact: Approximately 20 percent of the cases of breast cancer diagnosed every year are driven by abnormal signaling from the gene HER2 and are categorized as HER2-positive breast cancer. Dr. Drago is conducting studies to identify which patients may be responsive to treatment with an antibody drug conjugate (ADC) that targets the HER2 protein found on HER2-positive breast cancer cells. Antibody‐drug conjugates (ADCs) are being developed to selectively target cancer cells while sparing normal cells - these drugs are very potent and toxic. The results of these studies will improve patient outcome while avoiding potentially toxic side effects in patients that will not respond.
What’s next: Dr. Drago will develop methods to identify the biomarkers by microscopic examination of patients’ tumor samples and, in this way, determine which patients will potentially benefit from treatment with ADC, DS-8201a.
One of the most significant challenges in cancer treatment is finding medicines that target and kill cancer cells, but spare normal cells. One strategy that has been developed, called an antibody‐drug conjugate (ADC), attaches to the surface of cancer cells that express the antibody target – the cancer cells then swallow up the antibody as well as the drug attached. Dr. Drago is conducting studies to identify which patients may be responsive to treatment with a specific ADC that targets the HER2 protein to improve patient outcomes.
Full Research Summary
Research Area: Developing a method to predict which breast cancer cells will be sensitive to treatment with antibody-drug conjugates.
Impact: One of the most significant challenges in cancer treatment is finding medicines that target and kill cancer cells, but spare normal cells. Such treatments could allow for the selective destruction of cancer cells wherever they deposit inside the body without causing significant harm to normal cells and the resultant side effects. One strategy being developed to address this problem is called an antibody‐drug conjugate (ADC). The antibody component of ADCs attaches to a specific protein on the surface of cancer cells which then swallow up the antibody as well as the drug attached. Once the ADC is inside the cancer cell, it is digested by enzymes and the drug is released. Since these drugs are very potent and toxic to the cancer cell, the cancer cell is selectively killed. One of these new ADCs targets a protein called HER2 that is found on the surface of some breast cancer cells and, in fact, can detect breast cancers that have small amounts of HER2. Dr. Drago is conducting studies to identify which patients may be responsive to treatment with this ADC to improve patient outcome while avoiding potentially toxic side effects in patients that will not respond.
Current research: As part of his Conquer Cancer study, supported by BCRF, Dr. Drago and his colleagues are developing a system to predict which breast cancers will be sensitive to treatment with a previously developed ADC, DS‐8201a. While several treatments exist for the 15‐20 percent of breast cancers that have a large amount of HER2 on their surface, DS‐8201a was the first treatment of this kind to work in the 60 percent of breast cancers that only have a very small amount of HER2. DS‐8201a is unique in this way but is a powerful drug that has its own set of potential side effects - this limits its usefulness since physicians would be hesitant to recommend this drug to a patient who is unlikely to benefit. Therefore, it is necessary to identify methods to determine exactly which patients might benefit from receiving this treatment. Dr. Drago and his colleagues will utilize a new technique called multiplex immunofluorescence to find biomarkers that distinguish those tumors which will respond to treatment from those that will not. He hopes that the results of these studies will help to inform treatment decisions for patients with HER2-positive breast cancer.
Joshua Drago, MD is a fellow in Medical Oncology at Memorial Sloan Kettering Cancer Center, where he has developed a research focus on rational biomarker development and novel therapeutics in breast cancer. He is a graduate of Brown University and Harvard Medical School and completed his residency in Internal Medicine at Massachusetts General Hospital. Dr. Drago has been the recipient of the NIH Cancer Research Training Award, the ASCO/Conquer Cancer Foundation Merit Award, the Brian Piccolo Cancer Research Fellowship Award, the SABCS Coltman Scholars Award, and the METAvivor Early Career Investigator Award.