Breast cancer is the second most common form of cancer in women in the U.S. after skin cancer. It is characterized by the uncontrolled growth of tumor cells in the lobules, or milk ducts and often spreads to other parts of the body. According to statistics collected by the American Cancer Society (ACS), incident rates of breast cancer increase by 0.6% each year, and the average woman in the U.S. has a 1 in 8 chance of developing breast cancer at some point in her life, and an estimated 42,250 women will die from breast cancer this year.
Ductal carcinoma in situ (DCIS) is a non-invasive and more treatable form of breast cancer that affects only the milk ducts. This year, roughly 56,500 women will be diagnosed with DCIS, while around 310,720 women will be diagnosed with invasive breast cancer, which spreads beyond the milk ducts into surrounding tissue and can metastasize, affecting nearby organs. In response to these rising numbers, researchers from the Department of Chemistry and Chemical Biology are working with healthcare and cancer research organizations to discover innovative treatments for breast cancer.
Endocrine-based treatments of breast cancer suppress the hormone estrogen, which tumor cells need to grow. Drugs like tamoxifen “metabolizes into by-products which then bind to estrogen-receptor (ER) cells in breast tissue, out-competing the body’s natural hormones and preventing tumor-cell proliferation,” per an article released by the university. Treatments like this only work on 75% of patients, as tumor cells often grow immunity to these drugs, necessitating more toxic and invasive modes of treatment.
Chemistry professor Abhishek Sharma and his team have designed, developed, and tested a new class of molecules aimed at treating drug-resistant breast cancer. The team attached a bisphenol ligand, an estrogen receptor, to a “series of experimental side-chain compounds (known as degrons) the team hypothesized would hijack the cells’ normal protein-disposal machinery and direct them to break down the estrogen receptors.” Sharma has stated that the structure of these proteins has been tested using “nuclear magnetic resonance spectroscopy and mass spectrometry.” More than a dozen of the proteins have been tested in the labs of Memorial Sloan Kettering Cancer Center in New York and at the University of Illinois, and when the developed molecules came in contact with tumors, they were successful in stopping their growth. More work is being done, but these findings have been reported in a study published in the journal ACS Medicinal Chemistry Letters.
In another approach, researchers have examined the stiffness and extracellular matrix (ECM) surrounding breast tumors to see how their growth is influenced. Professor Hongjun Wong, head of the Department of Biomedical Engineering, and his team have expanded on this approach by developing a “proprietary semi-synthetic fiber/gel hybrid material that more closely models the actual environment in which cancer cells grow.” This material can be tuned to mimic stiff cancerous tissue as well as softer healthy tissue and all others around the area. Doctoral Candidate Mary Stack, who works on this project, defends this approach by stating that the team “needed something that was much more like the true extracellular matrix found in humans.”
The team then cultured two lines of lethal breast cancer cells in this fluid for several days and found that stiffer tissue surrounding a tumor fosters quicker growth while softer tissue slows it down. This level of understanding can be applied to medical interventions, as therapies can be developed to “actively target the properties of the extracellular matrix neighboring a tumor, rather than merely tumors themselves.” Medications can be developed to lessen the stiffness of the ECM of cells as a way of slowing their growth rather than attacking the tumors directly. This research was presented at the Biophysical Society’s annual conference in San Francisco in February, and the team hopes to publish these findings in a scientific journal by the end of this year.
Breast cancer research at Stevens is making large improvements that will impact healthcare for those affected. The innovative studies, which also involve scientists and physicians around the world, find new ways of examining the properties of tumor cells and provide less invasive and less risky modes of treating cancer.
