Poster Session 6, 4:15 PM - 5:00 PM: Campus Center Auditorium [A35]

Overcoming Multidrug Resistance Through Targeted Protein Degradation

Presenter: Jenny He

Faculty Sponsor: S. Thai Thayumanavan

School: UMass Amherst

Research Area: Cancer Studies

ABSTRACT

As one of the leading causes of death worldwide, cancer faces several therapeutic hurdles. Chemotherapy is one of the more popular treatment methods, but its potency is often diminished by the development of multidrug resistance (MDR) in cancer cells. MDR is a multifaceted issue that involves the intertwined interaction of several molecular pathways and is still not well understood. One such pathway involves ATP-binding cassette (ABC) transporters, which are efflux pump proteins that remove chemicals from the cytosol. Efflux pump P-glycoprotein (P-gp) is one of the more researched contributors to MDR, but it falls short as a target due to poor specificity. Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) serves as a potential alternative target for novel therapeutics to overcome MDR. Compared to P-gp, ROR1 is highlighted as a superior target due to its expression in primarily cancer cells as well as the role it plays in several drug resistance pathways. Current therapeutic strategies to reverse MDR through ROR1 inhibition are also summarized and evaluated. This review describes the molecular mechanisms that make the cure to cancer so elusive, provides background on the shortcomings of modern chemotherapeutics, compares P-gp and ROR1 as targets for combating MDR, and provides context for current development of treatment approaches that target ROR1.

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