The role of tumor hypoxia in the acquisition of resistance to microtubule-targeting drugs

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Hypoxia is one of the major factors causing resistance to microtubule-stabilizing drugs (MSDs) and other non-microtubule drugs used in chemotherapy. Hypoxia results in changes in tubulin conformation, expression of tubulin isotypes and metabolic pathways that make cancer cells less susceptible to paclitaxel, a taxane used extensively in the treatment of solid tumors. Recent cellular studies have shown that non-taxane MSDs with a similar mode of microtubule stabilization to paclitaxel is more effective in hypoxic cancer cells than paclitaxel. Due to a different microtubule-binding site, we hypothesize that non-taxane MSDs may have a better cytotoxic effect in cancer cells under hypoxia. The goal of this project is to study the anti-cancer effect of non-taxane MSDs in hypoxic ovarian and cervical cancer cell models.