Can We Use Chemotherapy Better in Order to Cure Triple Negative Breast Cancer?

Patients with cancer die because cells metastasis and resist therapy. I strongly believe that the cure to cancer will come from studying these biological processes. My lab studies breast cancer and the traits that make them more metastatic and less sensitive to current chemotherapies. I began my humble research career at James Madison University where I studied biology, biochemistry and crab digestive enzymes. Enthralled with the challenges of research and thrill of discovery, I attended Case Western Reserve University where I obtained my PhD degree in molecular biology studying how integrins cooperate with transforming oncogenes to promote cancer. During my studies, I noted that cancers of epithelial origin constitute the majority of cancer deaths. Accordingly, I wanted to study integrins that were responsible for the progression of these cancers. This interest took me to Harvard Medical School and the lab of Art Mercurio where I developed my interests in triple negative breast cancer (TNBC). I was fortunate to obtain my first faculty position at the University of Texas Medical Branch in Galveston in the Department of Surgery. The interactions with clinicians and other basic scientists drove my desires to work on clinically important questions and translate these finding to the clinic. At the UK Markey Cancer Center, I use these skills and passions to drive my research and direct our Breast Translational Group, which has thrived under my leadership. Through this group, I network with colleagues to find new ways to help patients with TNBC, the most lethal of the major breast cancer subtypes. I also developed my interests in mentoring other scientists and educating our next generation of scientists; my success in these areas led to my appointment as the Associate Director for Cancer Education and Mentoring. I believe my research expertise and my dedication to cancer education has made me a role model for other women scientists and a strong candidate for this Markey Women Strong Award. In my proposed research for this application, I will explore a concept that, if true, could lead to a clinical trial that could prevent metastatic recurrence of TNBC in patients with stage II or stage III disease. This concept is based on two studies. The first comes from my lab’s research showing that integrin α6β4, a protein on the cell surface of tumor cells that makes TNBC more aggressive, actually helps tumor cells respond to the drug cyclophosphamide, which is used to treat TNBC. We find when patients have a lot of integrin α6β4, they live. Metaplastic breast cancers, which do not express integrin α6β4, are rare, deadly cancers that are driven by cancer stem cells. Cancer stem cells are believed to cause metastases and recurrence that ultimately lead to the death. Dr. Ed Romond has found a curative therapy combination that is given weekly that cures them. I proposed to test if Dr. Romond’s therapy kills stem cells specifically, and if it does, we will work with our colleagues in the Markey Cancer Center to launch a clinical trial to test if this new approach that when combined with current standard treatment of TNBC with cyclophosphamide plus doxorubicin, can cure patients with TNBC by preventing stem cells from escaping treatment and growing into life threatening metastases.