Drug Combinations for Targeting Breast Cancer Cell Plasticity

Jarrett Childress*, Michael Ruppert, M.D., Ph.D.
WVU Cancer Institute Research Laboratories, West Virginia University, Morgantown, WV 26505

Presentation Category: Science & Techonology (Oral Presentation)

Student’s Major: Exercise Physiology

Cancer cell plasticity is promoted by cross-talk between three major embryonic stem cell (ESC)-like transcription factor networks: Core, Myc, and PRC2. These three major transcription factor networks are conserved between normal stem cells and cancer cells, suggesting a potential strategy for targeting the stem-like properties of cancer cells. These three networks are especially highly conserved in human cancer types that express strong ESC signatures such as basal-like breast cancer. When cancer cells are exposed to a variety of therapeutic agents, ranging from conventional chemotherapy to molecularly-targeted small molecules, they rapidly develop resistance through a type of epigenetic reprogramming. We propose that the three conserved transcription factor networks play a critical role in this process, conferring plasticity to cancer cells and leading to tumor cell survival and recurrence. By co-targeting these three networks we will address the functional redundancy that is common in ESC signaling. We have developed a strategy to rapidly screen all possible three-drug combinations from a set of 12 agents. We anticipate that specific combinations of drugs will induce differentiation, growth arrest and/or cell death.

Funding: Not funded

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course