SUMMARY
The research of Tony B. D'Assoro, M.D., Ph.D., focuses on characterizing the molecular mechanisms that cause key oncogenic pathways to induce cancer cell plasticity and breast cancer progression. Dr. D'Assoro's research team uses a wide variety of standard molecular, cell biology and biochemistry approaches and cutting-edge techniques to address the role of epithelial to mesenchymal transition (EMT) nuclear reprogramming. This reprogramming promotes cancer cell plasticity and the emergence of cancer stem cells with increased capacity for tumor self-renewal, intrinsic drug resistance and ultimately emergence of organ metastasis.
Dr. D'Assoro's translational cancer research mainly focuses on discovering key druggable stemness oncogenic pathways that will lead to the development of innovative early phase 1 and phase 2 clinical trials tailored to patients with advanced breast cancers that are refractory to standard-of-care therapies.
Focus areas
- Role of aurora-A mitotic kinase (AURKA) in EMT and tumor stemness. Dr. D'Assoro's research team is researching stemness-targeted therapies to inhibit the development of EMT, cancer cell plasticity and organ metastasis. The team was among the first to discover a novel nonmitotic role for AURKA in the development of EMT-mediated cancer cell plasticity, tumor stemness and endocrine resistance in breast cancer. Dr. D'Assoro is studying the pivotal role of AURKA in the nuclear reprogramming of cancer stem cells that express intratumoral PD-L1 and develop immune evasion and organ metastasis. Based on Dr. D'Assoro's preclinical studies, two clinical trials with an AURKA inhibitor, alisertib, have been completed in patients with estrogen receptor-positive cancer.
- Role of NOTCH3 signaling pathway in metastasis. Dr. D'Assoro's research team also is studying the role of the NOTCH3 signaling pathway in promoting the enrichment of metastasis-initiating cells with high self-renewal and immune evasion capacity that can induce early organ metastasis in triple-negative breast cancer. Dr. D'Assoro is investigating new therapeutic strategies to selectively target the NOTCH3 signaling pathway in clinically relevant triple-negative breast cancer models. These preclinical studies will lead to first-in-human clinical trials with selective NOTCH3 inhibitors in patients with advanced triple-negative breast cancers that resist standard-of-care chemotherapy and show limited response to immune checkpoint inhibitors approved by the U.S. Food and Drug Administration.
Significance to patient care
Dr. D'Assoro's cancer research will play a critical role in learning more about how cancer cells acquire a more aggressive phenotype that causes resistance to anticancer drugs and progression of breast cancer. Dr. D'Assoro's research team is working to find and develop innovative, targeted drug therapies to treat patients with advanced breast cancer that does not respond to standard therapies. The new therapies could benefit hundreds of thousands of women each year.