Mechanisms of Taxane 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.

A Comprehensive RNA Study to Identify circRNA and miRNA Biomarkers for Docetaxel Resistance in Breast Cancer

“…This gene has been implicated in various biological processes, including cancer development and progression (62,63). Recent studies have shown that EPHA3 is down-regulated in chemotherapy-resistant ovarian cancer cells (38) and implicated in regulation of multidrug resistance in small cell lung cancer via the PI3K signaling pathway, which has been frequently linked to taxane resistance (39,64). High expression of circEPHA3.1 and circEPHA3.2 in docetaxel-sensitive breast cancer cells, and their depletion in DRBC cells, indicates that these two circRNAs may be involved in maintaining docetaxel sensitivity in breast cancer cells.…”

MicroRNAs as Epigenetic Determinants of Treatment Response and Potential Therapeutic Targets in Prostate Cancer

“…Chemotherapy is the therapeutic option offered to mCPRC patients who have failed other treatment approaches and is mainly based on the use of taxanes (docetaxel, cabazitaxel). Resistance to these drugs is a multifactorial phenomenon in which alterations of microtubule regulatory proteins and tubulin isotopes play a major role [ 122 ].…”

Cytoskeletal Control and Wnt Signaling—APC’s Dual Contributions in Stem Cell Division and Colorectal Cancer

“…Other chemotherapeutic agents widely used are taxanes (e.g., paclitaxel or docetaxel), which stabilise microtubules, disrupt mitosis and cell cycle progression [ 117 ]. However, taxane resistance has been a drawback [ 118 ]. Recent combinatorial approaches between taxanes and small molecules that inhibit Wnt seem to have the potential to combat the resistance by synergising mitotic blockade [ 108 , 118 ].…”

“…However, taxane resistance has been a drawback [ 118 ]. Recent combinatorial approaches between taxanes and small molecules that inhibit Wnt seem to have the potential to combat the resistance by synergising mitotic blockade [ 108 , 118 ]. One of this Wnt inhibitors is ipafricept (OMP-54F28).…”