Abstract
Docetaxel (DTX) chemotherapy offers excellent initial response and confers significant survival benefit in patients with castration-resistant prostate cancer (CRPC). However, the clinical utility of DTX is compromised when primary and acquired resistance are encountered. Therefore, a more thorough understanding of DTX resistance mechanisms may potentially improve survival in patients with CRPC. This review focuses on DTX and discusses its mechanisms of resistance. We outline the involvement of tubulin alterations, androgen receptor (AR) signaling/AR variants, ERG rearrangements, drug efflux/influx, cancer stem cells, centrosome clustering, and phosphoinositide 3-kinase/AKT signaling in mediating DTX resistance. Furthermore, potential biomarkers for DTX treatment and therapeutic strategies to circumvent DTX resistance are reviewed.
Highlights
Prostate cancer (PCa) is one of the most common malignancies worldwide
This review presents molecular mechanisms related to DTX resistance [Table 1], potential biomarkers, and therapeutic strategies to improve survival in MECHANISMS OF RESISTANCE TO DOCETAXEL IN PROSTATE CANCER
Recent studies have shown that the increased expression of androgen receptor (AR)-v7 is associated with a worse prognosis in circulating tumor cells (CTCs) expressed in metastatic castration-resistant prostate cancer (CRPC) treated with taxanes, including DTX . [37,38] On the contrary, another study showed no significant association between AR-v7 expression and the efficacy of DTX in CTCs[39]
Summary
Prostate cancer (PCa) is one of the most common malignancies worldwide. In 2018, it was estimated that there were 1,200,000 new cases and 350,000 men died due to PCa[1]. Drug efflux and influx[48,49,50,53,54,55,56,57,60,61,62] ABCB1 expression is up-regulated in DTX-resistant PCa cell lines. SLCO1B3 expression is down-regulated in DTX-resistant PCa cell lines 5. One study has shown that a mutation (F270I) in the drug binding sites of the βI-tubulin gene was discovered in DTX-resistant PCa cell lines, conferring resistance to DTX[16].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
