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Mohamed A. A. A. Hegazi 1, Matteo Zanoni 3, Paolo Vota 3, Giovanni Toia 3, Maria Chiara Clementi 3, Cinzia Mazzieri 3, Maurizio Chiriva-Internati 4 and Gianluigi Taverna 2,3  \nCitation: Grizzi, F.; Hegazi,  \nM.A.A.A.; Zanoni, M.; Vota, P.; Toia, G.; Clementi, M.C.; Mazzieri, C.; Chiriva-Internati, M.; Taverna, G. Prostate Cancer Microvascular Routes: Exploration and Measurement Strategies. Life 2023, 13, 2034. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)life13102034  \nAcademic Editors: Paula A. Oliveira and Ana Faustino  \nReceived: 6 September 2023  \nRevised: 5 October 2023  \nAccepted: 7 October 2023  \nPublished: 9 October 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Rozzano,  \n20089 Milan, Italy; [lunamohamed75@gmail.com](lunamohamed75@gmail.com)  \n2 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy;  \ngianluigi.taverna@humanitas.it  \n3 Department of Urology, Humanitas Mater Domini, Castellanza, 21053 Varese, Italy; [matteo.zanoni@materdomini.it](matteo.zanoni@materdomini.it) (M.Z.); [paolo.vota@materdomini.it](paolo.vota@materdomini.it) (P.V.); [giovanni.toia@materdomini.it](giovanni.toia@materdomini.it) (G.T.); mariachiara.clementi@mc.humanitas.it (M.C.C.); [cinzia.mazzieri@materdomini.it](cinzia.mazzieri@materdomini.it) (C.M.)  \n4 Departments of Gastroenterology, Hepatology & Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [mnchiriva@mdanderson.org](mnchiriva@mdanderson.org)  \n* Correspondence: fabio.grizzi@humanitasresearch.it  \nAbstract: Angiogenesis is acknowledged as a pivotal feature in the pathology of human cancer. Despite the absence of universally accepted markers for gauging the comprehensive angiogenic activity in prostate cancer (PCa) that could steer the formulation of focused anti-angiogenic treatments, the scrutiny of diverse facets of tumoral blood vessel development may furnish significant understanding of angiogenic processes. Malignant neoplasms, encompassing PCa, deploy a myriad of strategies to secure an adequate blood supply. These modalities range from sprouting angiogenesis and vasculogenesis to intussusceptive angiogenesis, vascular co-option, the formation of mosaic vessels, vasculogenic mimicry, the conversion of cancer stem-like cells into tumor endothelial cells, and vascular pruning. Here we provide a thorough review of these angiogenic mechanisms as they relate to PCa, discuss their prospective relevance for predictive and prognostic evaluations, and outline the prevailing obstacles in quantitatively evaluating neovascularization via histopathological examinations.  \nKeywords: prostate cancer; vasculature; microvessel density; biomarkers; fractals  \n1. Introduction  \nCancer research has undergone radical changes in recent years [1] . The challenge now is not the volume of foundational and clinical data at our disposal, but rather the management and interpretation of this surfeit of information. In spite of these advancements, prostate cancer (PCa) continues to pose a substantial global public health concern [2,3] . Cancers of the prostate, lung, and bronchus, as well as colorectal cancers, collectively constitute nearly half of all new male cancer cases, with PCa alone responsible for 27% of these diagnoses [4] . Critical to tumor expansion, advancement, and the metastatic spread of cancer cells is the availability of blood supply. New blood","cbCailmLfVKmqV3a","https://ap.wps.com/l/cbCailmLfVKmqV3a","pdf",1754195,23,"English","# Abstract\n# Introduction\n## Angiogenesis in cancer and physiology\n## Regulation by pro- and anti-angiogenic factors\n## Historical background of angiogenesis","[{\"question\":\"Why are angiogenesis markers important in prostate cancer?\",\"answer\":\"The review notes that prostate cancer has no universally accepted markers to gauge comprehensive angiogenic activity, limiting the development of focused anti-angiogenic treatments.\"},{\"question\":\"What angiogenic mechanisms are covered as relevant to prostate cancer?\",\"answer\":\"It reviews several vessel-development strategies, including sprouting angiogenesis, vasculogenesis, intussusceptive angiogenesis, vascular co-option, mosaic vessels, vasculogenic mimicry, conversion of cancer stem-like cells into tumor endothelial cells, and vascular pruning.\"},{\"question\":\"What makes quantitative histopathological assessment of neovascularization challenging?\",\"answer\":\"The paper outlines obstacles in quantitatively evaluating neovascularization via histopathological examinations and frames these gaps as part of the broader need for better assessment strategies.\"}]","Prostate Cancer Microvascular Routes: Exploration and Measurement Strategies - Review | PDF",1790229668,58]