Abstract
Prostate cancer (PCa) is a malignant disorder of prostate gland being asymptomatic in early stages and high metastatic potential in advanced stages. The chemotherapy and surgical resection have provided favourable prognosis of PCa patients, but advanced and aggressive forms of PCa including CRPC and AVPC lack response to therapy properly, and therefore, prognosis of patients is deteriorated. At the advanced stages, PCa cells do not respond to chemotherapy and radiotherapy in a satisfactory level, and therefore, therapy resistance is emerged. Molecular profile analysis of PCa cells reveals the apoptosis suppression, pro-survival autophagy induction, and EMT induction as factors in escalating malignant of cancer cells and development of therapy resistance. The dysregulation in molecular profile of PCa including upregulation of STAT3 and PI3K/Akt, downregulation of STAT3, and aberrant expression of non-coding RNAs are determining factor for response of cancer cells to chemotherapy. Because of prevalence of drug resistance in PCa, combination therapy including co-utilization of anti-cancer drugs and nanotherapeutic approaches has been suggested in PCa therapy. As a result of increase in DNA damage repair, PCa cells induce radioresistance and RelB overexpression prevents irradiation-mediated cell death. Similar to chemotherapy, nanomaterials are promising for promoting radiosensitivity through delivery of cargo, improving accumulation in PCa cells, and targeting survival-related pathways. In respect to emergence of immunotherapy as a new tool in PCa suppression, tumour cells are able to increase PD-L1 expression and inactivate NK cells in mediating immune evasion. The bioinformatics analysis for evaluation of drug resistance-related genes has been performed.
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Acknowledgements
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Milad Ashrafizadeh and Wei Zhang contributed in writing first draft of paper and drawing figures. Yu Tian performed bioinforamtics analysis. Gautam Sethi and Xianbin Zhang developed idea, collected papers and edited paper. Aiming Qiu revised the paper, improved the quality and language, reduced the plagiarism, replaced and drew new and high quality figures and added the tables.
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Highlights
• The drug resistance development in prostate cancer (PCa) has resulted in therapy failure in patients.
• Abnormal biological mechanisms including apoptosis, autophagy, and EMT mediate chemoresistance.
• Dysregulation of molecular pathways induces both chemoresistance and radioresistance in PCa.
• Pharmacological compounds and nanostructures increase therapy sensitivity.
• Immune evasion compromises function of immunotherapy in PCa suppression.
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Ashrafizadeh, M., Zhang, W., Tian, Y. et al. Molecular panorama of therapy resistance in prostate cancer: a pre-clinical and bioinformatics analysis for clinical translation. Cancer Metastasis Rev 43, 229–260 (2024). https://doi.org/10.1007/s10555-024-10168-9
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DOI: https://doi.org/10.1007/s10555-024-10168-9