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

Published on May 14, 2021in Cancers6.126
· DOI :10.3390/CANCERS13102380
Valentina Doldi8
Estimated H-index: 8
Rihan El Bezawy3
Estimated H-index: 3
Nadia Zaffaroni66
Estimated H-index: 66
Prostate cancer (PCa) is the second most common tumor in men worldwide, and the fifth leading cause of male cancer-related deaths in western countries. PC is a very heterogeneous disease, meaning that optimal clinical management of individual patients is challenging. Depending on disease grade and stage, patients can be followed in active surveillance protocols or undergo surgery, radiotherapy, hormonal therapy, and chemotherapy. Although therapeutic advancements exist in both radiatiotherapy and chemotherapy, in a considerable proportion of patients, the treatment remains unsuccessful, mainly due to tumor poor responsiveness and/or recurrence and metastasis. microRNAs (miRNAs), small noncoding RNAs that epigenetically regulate gene expression, are essential actors in multiple tumor-related processes, including apoptosis, cell growth and proliferation, autophagy, epithelial-to-mesenchymal transition, invasion, and metastasis. Given that these processes are deeply involved in cell response to anti-cancer treatments, miRNAs have been considered as key determinants of tumor treatment response. In this review, we provide an overview on main PCa-related miRNAs and describe the biological mechanisms by which specific miRNAs concur to determine PCa response to radiation and drug therapy. Additionally, we illustrate whether miRNAs can be considered novel therapeutic targets or tools on the basis of the consequences of their expression modulation in PCa experimental models.
Prostate cancer (PCa) is the fifth cause of tumor-related deaths in man worldwide. Despite the considerable improvement in the clinical management of PCa, several limitations emerged both in the screening for early diagnosis and in the medical treatment. The use of prostate-specific antigen (PSA)-based screening resulted in patients’ overtreatment and the standard therapy of patients suffering from locally advanced/metastatic tumors (e.g., radical prostatectomy, radiotherapy, and androgen depriv...
1 CitationsSource
#1Nicolas MottetH-Index: 40
Last. Philip Cornford (University of Liverpool)H-Index: 27
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Abstract Objective To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa). Evidence acquisition The panel performed a literature review of new data, covering the tim...
44 CitationsSource
#1Philip Cornford (University of Liverpool)H-Index: 27
Last. Nicolas MottetH-Index: 40
view all 27 authors...
Abstract Objective To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). Evidence acquisition The working panel performed a literature review of the new data (2016–2...
41 CitationsSource
#1Zhenhua He (Lanzhou University)H-Index: 4
#2Fuhui Shen (Lanzhou University)H-Index: 1
Last. Zhiping Wang (Lanzhou University)H-Index: 20
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Heat shock protein 27 (HSP27), a regulator of cell survival, can enhance the resistance of cancer cells to radiotherapy. As microRNA-541-3p (miR-541-3p) was recently predicted to be a putative upstream modulator of HSP27, the present study was designed to investigate the function and mechanism underlying how miR-541-3p modulates the radiosensitivity of prostate cancer (PCa) cells by regulating HSP27. Through quantitative PCR, miR-541-3p was determined to be poorly expressed in PCa tissues relati...
1 CitationsSource
#1Norman J. Maitland (Ebor: University of York)H-Index: 61
Increasingly sophisticated therapies for chemical castration dominate first-line treatments for locally advanced prostate cancer. However, androgen deprivation therapy (ADT) offers little prospect of a cure, as resistant tumors emerge rather rapidly, normally within 30 months. Cells have multiple mechanisms of resistance to even the most sophisticated drug regimes, and both tumor cell heterogeneity in prostate cancer and the multiple salvage pathways result in castration-resistant disease relate...
3 CitationsSource
#1Yasutaka Yamada (Harvard University)H-Index: 1
#2Himisha Beltran (Harvard University)H-Index: 57
PURPOSE OF REVIEW Neuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype of prostate cancer that most commonly arises in later stages of prostate cancer as a mechanism of treatment resistance. The poor prognosis of NEPC is attributed in part to late diagnosis and a lack of effective therapeutic agents. Here, we review the clinical and molecular features of NEPC based on recent studies and outline future strategies and directions. RECENT FINDINGS NEPC can arise "de novo" but mo...
5 CitationsSource
#1Sara M. MaloneyH-Index: 2
#2Camden A. Hoover (ND: University of Notre Dame)H-Index: 2
Last. Jenifer R. ProsperiH-Index: 13
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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 ...
5 CitationsSource
#1Theresa AkotoH-Index: 2
#2Divya BhagirathH-Index: 6
Last. Sharanjot Saini (Georgia Regents University)H-Index: 3
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Prostate cancer is a condition commonly associated with men worldwide. Androgen deprivation therapy remains one of the targeted therapies. However, after some years, there is biochemical recurrence and metastatic progression into castration-resistant prostate cancer (CRPC). CRPC cases are treated with second-line androgen deprivation therapy, after which, these CRPCs transdifferentiate to form neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. NEPC arises via a reversibl...
#1Divya BhagirathH-Index: 6
#2Michael Liston (UCSF: University of California, San Francisco)H-Index: 1
Last. Sharanjot Saini (Georgia Regents University)H-Index: 3
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Therapy-induced neuroendocrine prostate cancer (NEPC), an extremely aggressive variant of castration-resistant prostate cancer (CRPC), is increasing in incidence with the widespread use of highly potent androgen receptor (AR)-pathway inhibitors (APIs) such as Enzalutamide (ENZ) and Abiraterone and arises via a reversible trans-differentiation process, referred to as neuroendocrine differentiation (NED). The molecular basis of NED is not completely understood leading to a lack of effective molecu...
3 CitationsSource
#1Yongheng YeH-Index: 1
#2Lingli ZhangH-Index: 1
Last. Peiheng HeH-Index: 1
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Objective This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro. Methods A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG....
1 CitationsSource
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