Mechanisms of Taxane Resistance

SIMPLE SUMMARY: Drug resistance is prevalent in many types of cancer and decreases patient survival. The taxanes are anti-mitotic chemotherapeutic agents, widely used since the 1990s to treat many types of cancer. Even with the popularity of the taxane family, many patients are, or will become, resistant to taxane treatment, meaning that other, perhaps less effective, treatment options are required. This review article seeks to provide information about the common cancers in which taxanes are used and resistance occurs, in order to find targetable mechanisms that can be used to overcome resistance. ABSTRACT: The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug–inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.