Abhishek Sharma, a chemistry professor in Stevens Institute of Technology’s Department of Biomedical Engineering, Chemistry and Biological Sciences, was awarded a grant by Susan G. Komen foundation.
The grant will cover 3 years of research into developing novel anti-breast cancer agents. Specifically, it will cover the discovery and development of organic compounds capable of effectively blocking the activity of estrogen receptors in drug-resistant forms of breast cancer.
“One of the most common causes of breast cancer is increased stimulation of breast tumor cells by the action of estrogen on estrogen receptors (ERs) found in many of these cancers,” Sharma writes in the proposal abstract. He continues, describing the particular difficulty of breast cancer:
Estrogen stimulates these cancer cells by binding to a specific pocket in the ER (the ligand binding pocket, LBP), forming an ER-estrogen complex that is able to bind to some important accessory proteins called coactivators. The newly formed ER-coactivator complexes can interact with DNA, turning on cellular processes that stimulate tumor cells to grow.
One serious complication with breast cancer patients is that even after initial successful treatment, the cancer often returns and spreads. That’s known as metastasis. Metastatic breast cancer is resistant to all medication currently on the market. One drug, tamoxifen, has been shown to block estrogen binding to the LBP and prevent the formation of the ER-coactivator complex. But tamoxifen is not effective against metastatic forms of breast cancer.
Sharma is trying to create a better drug. As he put it:
The goal of my research is to develop novel estrogen receptor antagonists that target one of the major pathways responsible for development of drug resistance in breast cancer. Recent studies have shown that mutations in the LBP of ER allow these ERs to automatically switch from the “off” to the “on” state, leading to the hormone independent formation of ER-coactivator complex.
“We are developing molecules that specifically and potently block the formation of mutant ER-coactivator complexes,” he continued. This research work involves techniques such as synthetic organic chemistry and computational modeling.
Sharma certainly has the experience to do it. He did his post-doctoral research at the University of Illinois, where he worked with leading scientists who made fundamental contributions to the medicinal chemistry and pharmacology of estrogen receptors.
Ultimately, Sharma hopes that his “novel ER antagonists will offer a safer therapeutic alternative to patients with endocrine-resistant breast cancer by sparing them treatment with chemotherapeutics that have toxic side-effects,” according to the proposal.
Solving that problem ties in nicely to the Komen Foundation’s mission to fund research with the potential to reduce mortality associated with, and ultimately end, breast cancer. The Komen Foundation is the world’s largest breast cancer organization, funding more breast cancer research than any other nonprofit. Sharma’s grant was awarded after a highly rigorous peer-review.
