dong zhao - chemistry and materials science phd defense

dong dong zhao will present her phd research on monday, aug. 12 at 9 a.m. in cb 4058 and on zoom.

title - design, synthesis, and evaluation of novel aurora kinase inhibitors for cancer diagnosis and therapy

cancer remains the second leading cause of death globally, with advancements in diagnosis and therapeutics playing a crucial role in improving patient outcomes. aurora kinases, as essential mitotic regulators, have been key targets in cancer treatment due to their oncogenic properties. despite the development of various selective and pan-aurora inhibitors demonstrating effective antitumor properties in preclinical studies, none have been approved for human use. the need for novel, highly selective inhibitors is critical for advancing cancer therapy and understanding the biological functions of aurora kinases. aurora kinase a, b, and c, though structurally similar, differ in subcellular locations and cancer-specific amplification. inhibiting aurora a poses risks of secondary tumors, whereas targeting aurora kinase b with selective inhibitors offers a less toxic strategy. this research focusing on the most potent aurora b inhibitor, barasertib, has revealed that enhancing specific residue interactions could improve selectivity for aurora b over a. further developments led to a new inhibitor with high selectivity for aurora b and significant anticancer activity against hpv-positive cervical cancer cell lines. additionally, efforts to create potent 18f-radiotracers for cancer imaging have shown improved binding affinity. the structural selectivity mechanism of the first aurora c inhibitor, hce0063, aids in distinguishing between aurora b and c due to their phenotypic similarities. an overview of cancer metastasis, its cellular and molecular mechanisms, and recent advances in anti-metastatic strategies were also discussed. this research enhances the understanding of aurora kinase inhibitors' structural selectivity and therapeutic potential, paving the way for the development of highly selective and potent inhibitors for cancer diagnosis and treatment.

supervisory committee: dr. jinqiang hou and dr. christine gottardo (co-supervisors), dr. mike campbell, dr. wely floriano, dr. justin jiang, dr. yifeng li (external), dr. rob mawhinney (chair)

please contact brenda magajna at phd.ses@lakeheadu.ca for more information or the zoom link.