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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 progression. 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.

 

Comments:

Prostate cancer is a serious medical condition that is often diagnosed at an advanced stage due to the lack of specific symptoms in its early stages. As a result, tumor cells display a low response to chemotherapy, and genomic mutations in prostate cancer can enhance the aggressiveness of tumor cells. Docetaxel and paclitaxel are two common compounds used in chemotherapy for prostate cancer that function by inhibiting the depolymerization of microtubules, impairing the balance of microtubules, and delaying cell cycle progression. However, resistance to these compounds can develop in prostate cancer, which reduces their effectiveness.

One mechanism of resistance to chemotherapy in prostate cancer involves the upregulation of oncogenic factors, such as CD133, and the downregulation of tumor-suppressor genes, such as PTEN. This can enhance the malignancy of prostate tumor cells and induce drug resistance. Therefore, understanding these mechanisms is crucial in developing new strategies for overcoming drug resistance in prostate cancer.

One approach for enhancing drug sensitivity in prostate cancer is the use of phytochemicals as anti-tumor compounds. Naringenin and lovastatin are examples of such compounds that have been used to suppress the progression of prostate tumors and enhance drug sensitivity.

In addition to phytochemicals, nanostructures such as polymeric micelles and nanobubbles have been utilized in delivering anti-tumor compounds and reducing the risk of chemoresistance development. These approaches provide new insight into reversing drug resistance in prostate cancer and offer promising options for the treatment of this disease.

Overall, a better understanding of the mechanisms of drug resistance in prostate cancer, as well as the use of novel approaches such as phytochemicals and nanostructures, can lead to the development of more effective therapies for this disease.

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