Paclitaxel and docetaxel resistance in prostate cancer: Molecular mechanisms and possible therapeutic strategies

Prostate cancer is among most malignant tumors around the world and this urological tumor can be developed as result of genomic mutations and their accumulation during progression towards advanced stage. Due to lack of specific symptoms in early stages of prostate cancer, most cancer patients are diagnosed in advanced stages that tumor cells display low response to chemotherapy. Furthermore, genomic mutations in prostate cancer enhance the aggressiveness of tumor cells. Docetaxel and paclitaxel are suggested as well-known compounds for chemotherapy of prostate tumor and they possess a similar function in cancer therapy that is based on inhibiting depolymerization of microtubules, impairing balance of microtubules and subsequent delay in cell cycle pro-gression. The aim of current review is to highlight mechanisms of paclitaxel and docetaxel resistance in prostate cancer. When oncogenic factors such as CD133 display upregulation and PTEN as tumor-suppressor shows decrease in expression, malignancy of prostate tumor cells enhances and they can induce drug resistance. Furthermore, phytochemicals as anti-tumor compounds have been utilized in suppressing chemoresistance in prostate cancer. Naringenin and lovastatin are among the anti-tumor compounds that have been used for impairing progression of prostate tumor and enhancing drug sensitivity. Moreover, nanostructures such as polymeric micelles and nanobubbles have been utilized in delivery of anti-tumor compounds and decreasing risk of chemoresistance development. These subjects are highlighted in current review to provide new insight for reversing drug resistance in prostate cancer.

Automated summary

Prostate cancer is a highly malignant tumor caused by genomic mutations. The lack of specific symptoms in early stages leads to late diagnosis and low response to chemotherapy. Docetaxel and paclitaxel inhibit depolymerization of microtubules and delay cell cycle progression, but resistance to these drugs can occur due to upregulation of oncogenic factors and downregulation of tumor suppressor genes. Phytochemicals such as naringenin and lovastatin have been used to impair tumor progression and enhance drug sensitivity. Nanostructures like polymeric micelles and nanobubbles have also been utilized to deliver anti-tumor compounds and reduce the risk of chemoresistance development. This review provides new insights for reversing drug resistance in prostate cancer.