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. 2018 ). Along with the AT release of adipokines that may contribute to tumor progression, extracellular vesicles (EVs) derived from obese AT also play a role in this scenario ( Robado de Lope et al. 2018 ). EVs are small membrane vesicles coated
Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan
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isolation, storage, recovery, and the characterization from biofluids, such as plasma, serum, or urine, need to be optimized and standardized for clinical applications. The International Society for Extracellular Vesicles recently provided guidelines for EV
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various malignancies, including PTC ( Khatami & Tavangar 2018 , Rappa et al. 2019 , Toraih et al. 2021 ). Special attention was paid to small non-coding RNAs, micro-RNAs (miRNAs), and small lipid bilayer-enclosed extracellular vesicles (EVs), both
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Poly (ADP-ribose) polymerase (PARP) inhibitors have antitumor activity in advanced prostate cancer associated with loss of homologous recombination repair (HRR) function. About 20% of all patients with advanced prostate cancer present germline or tumor mutations in HRR-related genes, the most common being BRCA2, mutated in approximately 10% of all advanced prostate cancers. Challenges related to sample availability, tumor heterogeneity and access to NGS technology need to be addressed for a successful implementation of genomic stratification in routine clinical practice. The recent regulatory approvals of PARP inhibitors olaparib and rucaparib represent the first molecular biomarker-guided drugs for men with prostate cancer. While these findings represent a significant advance in the field of precision medicine and prostate cancer, there are still many unsolved questions on the optimal use of PARP inhibitors in this disease. Several clinical trials have shown that different mutations in various genes are associated with distinct magnitudes of sensitivity to PARP inhibitors, with BRCA2 mutations associating with more frequent and durable responses, questioning the benefit for subset of patients with mutations in other HRR-associated genes. In this review, we scrutinize the clinical development of different PARP inhibitors for the treatment of advanced prostate cancer, and we discuss how the study of additional biomarkers and the design of rational drug combinations can maximize patient benefit from this drug class.
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Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
Perinatology Research Branch, NICHD/NIH, Wayne State University, Detroit, Michigan, USA
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Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, Queensland, Australia
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Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, Queensland, Australia
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Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
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and metastasis. At the beginning, cancer cells activate the endogenic oncogenic pathways and prompt the cells to proliferate in their local niches. Nevertheless, at some point, these cells recruit endogenous secretions, such as extracellular vesicles
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). Extracellular vesicles (EVs) derived from metastatic tumor cells can also be detected in the circulation in men with CRPC, including those that are CTC-negative, and may carry tumor-associated proteins that can be quantified and tracked serially ( Gerdtsson et
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). Exosomes are extracellular vesicles (diameter 30–150 nm) secreted by cells with various biological functions ( Mears et al. 2004 , Sharma et al. 2016 ). Their involvement in intercellular communication has been widely depicted by delivering signaling
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by regulating death signals, miRNAs can also mediate response to antiestrogens. Extracellular vesicular (exosomes) transport of miRNAs in endocrine resistance Extracellular vesicles (EVs), produced by outward budding of the PM, contain proteins and
CNRS UMR7275, Valbonne, France
NEOGENEX CNRS International Associated Laboratory, Valbonne, France
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France
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). This mechanism could also be relevant in ACC, where Wnt signaling activating mutations have been described to be the most frequent tumor mutations ( Assié et al . 2014 , Zheng et al. 2016 ). Extracellular vesicle-associated miR-483-5p isolated
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Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, UniversitätsSpital Zürich, Zürich, Switzerland
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composition of a subset of ACC. Traces of extracellular vesicle-associated microRNAs in the blood was also found to be useful but for a different purpose; perioperative diagnosis of ACC ( Perge et al . 2017 ). Translational research and basic science
