An innovative collaboration between the chemistry and biology departments at Southern could mean a breakthrough in the treatment of a common form of breast cancer, and a student researcher participating in this work is gaining valuable experience while making a contribution to the field of cancer treatment.
Chemistry Professor Gerry Lesley and student Scott Brossman have synthesized several new derivatives of tamoxifen, a treatment often given after surgery. Biology Professor Sarah Crawford is now testing those derivatives in her lab to see how well they address tamoxifen resistance in cancer cells.
For many patients, tamoxifen is and has been prescribed to prevent reoccurrence for as long as 10 years following surgery to remove tumors. Known as an “antiestrogen,” it blocks the activity of the hormone estrogen in the breast and may inhibit the recurrence of cancer cells that are estrogen receptor positive (ER+), meaning that their growth is fueled by the presence of estrogen.
Crawford has been researching the behavior and characteristics of cancer cells in her biology lab at Southern for decades and has a personal interest in wellness, nutrition, and cancer prevention. She is quick to point out that the term “breast cancer” actually refers to “a collection of diseases in the breast” that have a variety of characteristics — one of which is estrogen receptors.
“It is like a lock and key found in the breast cells. The estrogen receptor is the lock and estrogen is the key. Estrogen is a perfectly normal hormone, but when cells become abnormal then there become too many receptors and it opens too many doors too quickly,” Crawford explains. Tamoxifen is prescribed to block the key from opening the door. But over time, cancer cells become resistant to its effects.
“The problem is that the body adapts a resistance to it,” says Lesley. “And so there is a growing need for a second generation tamoxifen derivative.” Thus, he began researching the molecular structure of tamoxifen. Lesley points out that this interdisciplinary collaboration stemmed from casual conversation among colleagues and was exactly what the university intended when the Academic Sciences and Laboratory Building was constructed and opened in 2015.
Brossman, meanwhile, transferred to SCSU from Boston University during the height of the pandemic and was taking several classes remotely. When he began to feel he was falling behind, he reached out to Lesley, who “took a liking to me and gave me a tour of the lab” when Covid restrictions began to lift. Brossman has since taken a position as a student researcher as he works through the Accelerated Pathway program toward a master’s degree in chemistry.
Working with Lesley, Brossman has learned the techniques for the difficult synthesis of the tamoxifen derivatives. The two have created several possible variations using a Schlenk line, or vacuum gas manifold, that allows for several reactions under inert atmospheric conditions to run simultaneously. The derivatives are now being tested for effectiveness in the biology lab under Crawford’s supervision.
“We’ll be testing to see, Is there an effect? How much of an effect? What concentration is most effective? Is it toxic to normal cells? How does it compare to tamoxifen in a tamoxifen-resistant cell line?” Crawford explains. If it works, it expands the potential arsenal of medications used to treat ER+ breast cancer.
The goal is twofold: Lesley and Crawford are seeking a grant from the National Institutes of Health to create a summer research program that would allow for students to have paid opportunities to gain experience in the SCSU biology and chemistry labs where ground-breaking research is taking place. They are also hoping to seek a patent through a pharmaceutical company that will expand their research and begin the slow process of bringing a potential treatment to the level of human trials.
For Brossman, the whole experience has changed his personal goals a bit. While he was originally planning to go to medical school, he now sees a different pathway to helping people. He plans to continue in research and pharmacology. A close family friend has recently been diagnosed with breast cancer, and he says the diagnosis has made him more ambitious to be part of the solution.
“I think, through research, I can make more of a difference sooner than I would if I went to medical school,” Brossman says.