Deciphering Tumor Heterogeneity in Breast Cancer using Single-Cell Analysis

Overview

Knight Cancer Institute Breast cancer is the most common form of cancer and the second‐leading cause of cancer-related death in U.S. women. Up to 70% of all breast cancers are driven by the hormone estrogen. Hormone therapies that block estrogen from binding to cancerous breast cells have proved very effective, leading to high survival rates at 5 years. However, beyond 5 years, increased mortality rates are observed due to therapeutic failure. Literature has identified tumor heterogeneity as a major obstacle for effective hormone therapy. As cancer progresses, the breast tumor becomes more heterogeneous and consists of more diverse cells with distinct molecular signatures and differential levels of sensitivity to treatment. It is essential to decipher tumor heterogeneity to overcome therapeutic resistance and ultimately combat breast cancer. The purpose of this project is to decipher breast tumor heterogeneity and its underlying mechanisms through single-cell analysis. Analysis of single-cell RNA- sequencing data revealed that cancerous breast cells recapitulate healthy breast cell types and cycle between them. This plasticity allows the cancerous breast cells to escape hormone therapy. Through analysis of epigenetic data, transcription factor KLF4 emerged as a master regulator of this heterogeneity. By inhibiting KLF4, tumor cells can be prevented from evading hormone therapies through their plasticity. These previously undiscovered mechanisms of breast cancer heterogeneity and the corresponding putative master regulator KLF4 can help create the next generation of effective hormone therapy for breast cancer.

Competition history

• JSHS 2020 Category not listed

Resources

• National JSHS abstract book ↗

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