{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:17:10Z","timestamp":1790705830191,"version":"4.1.0"},"reference-count":262,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,5]],"date-time":"2021-09-05T00:00:00Z","timestamp":1630800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, including nutrients, oxygen, and growth signals, to the expanding tumor mass. Nerves and vessels are also fundamental for the process of metastatic spreading, as they provide both the pro-metastatic signals to the tumor and the scaffold through which cancer cells can reach distant organs. Not surprisingly, continuously growing attention is devoted to the development of therapies specifically targeting these structures, with promising initial results. In this review, we summarize the latest evidence that supports the importance of blood vessels and peripheral nerves in cancer pathogenesis, therapy resistance, and innovative treatments.<\/jats:p>","DOI":"10.3390\/cancers13174471","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T10:59:12Z","timestamp":1630925952000},"page":"4471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance"],"prefix":"10.3390","volume":"13","author":[{"given":"Niccol\u00f2","family":"Roda","sequence":"first","affiliation":[{"name":"Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Blandano","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Giuseppe","family":"Pelicci","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13578-017-0188-9","article-title":"Tumorigenesis as a process of gradual loss of original cell identity and gain of properties of neural precursor\/progenitor cells","volume":"7","author":"Cao","year":"2017","journal-title":"Cell Biosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Roda, N., Gambino, V., and Giorgio, M. 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