New therapies to treat metastatic breast cancer may lie within one of the most commonly used agents in health care across the world: antibiotics. Sonal Chaudhari, a second-year medical student at the Johns Hopkins University School of Medicine, recently spent her summer working under Richard Jones, director of the Bone Marrow Transplant Program, co-director of the Hematologic Malignancies Program and professor of oncology and medicine, deriving new ways to treat metastatic breast cancer using the everyday antibiotic, clarithromycin (sold under the brand Biaxin).
Chaudhari focused on the bone marrow microenvironment, which contains enzymes known as cytochrome P450 (CYP450) that have a protective effect on metastasized solid tumors coming from breast, lung, kidney and prostate tissue. When these tumors are exposed to chemotherapy drugs, the CYP450 enzymes can actually metabolize the drugs or change the bone marrow microenvironment before the drugs can target cancer cells, thus shielding the tumors from the effects of potent anticancer agents.
Incredibly, studies from Jones’ group have shown that the commonly used antibiotic clarithromycin has CYP450-inhibitory characteristics, and can block the effects of these enzymes, allowing chemotherapies given in conjunction with clarithromycin to effectively kill tumor cells. Specifically, Chaudhari discovered that the CYP450 enzymes in stromal cells have a protective effect on metastatic breast cancer in vitro. She is currently optimizing experiments to replicate this preliminary discovery. She also plans to elucidate the mechanisms by which specific CYP450 enzymes are protecting metastatic breast cancer cells, in hopes that she can specifically target molecules in future treatment therapies of metastatic breast cancer.
Building A Career in Academic Medicine
As part of the medical school curriculum, students are mandated to conduct some type of faculty-mentored scholarly concentration in the summer between the first and second year. Chaudhari chose to do basic science bench work, while other students can choose clinical projects centered on patient databases, ethics and art in medicine, public health and community service, or even the history of medicine.
When asked about the most rewarding aspect of this type of research, Chaudhari said that troubleshooting her experiments taught her many lessons: “I enjoy troubleshooting experiments and love trying different yet logical things to try to get my experiments to work optimally … although I am very meticulous and thorough with my experiments, they allow me chances to fail and troubleshoot, which has taught me, one, to ask for help from mentors whenever appropriate; two, to trust myself more; and, three, to value communication with patients more because, unlike my cells, my patients can hopefully communicate with me their concerns and feelings.”
Student research is a critical component of the school of medicine’s learning environment. With regard to her scholarly concentration, Chaudhari states, “This summer has definitely been a positive experience, so I definitely envision working in basic science labs during residency and/or fellowships in the future.” Chaudhari is not entirely sure about her professional path yet, but knows that she will choose a path that allows her to use her basic science skills toward medical research. “I aspire to build my career in academic medicine,” she says, “and it has been my dream to incorporate basic and translational research into my career path.”
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