{"id":1208,"date":"2025-01-25T20:42:45","date_gmt":"2025-01-25T20:42:45","guid":{"rendered":"https:\/\/staging.irccs.com\/?post_type=laboratory&p=1208"},"modified":"2025-11-11T17:05:00","modified_gmt":"2025-11-11T17:05:00","slug":"vascular-oncology","status":"publish","type":"laboratory","link":"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/","title":{"rendered":"VASCULAR ONCOLOGY"},"content":{"rendered":"\n

<\/span>Research topic<\/h2>\n\n\n\n

Tumor microenvironment (TME) includes immune and stromal cells, blood vessels, nerves and extracellular matrix.  The Lab is interested in analyzing the  circuits between cancer cells and TME orchestrated by the transcription factor EB (TFEB)  and understanding their roles in disease progression and therapeutic responses, with an emphasis on pancreatic ductal adenocarcinomas (PDAC) and melanomas.<\/p>\n\n\n\n

<\/span>Background<\/h2>\n\n\n\n

Tumor cells reshape cellular phenotypes  within their host tissues. The appearing TME is continuously evolving  and assumes pro- or anti-tumor activities.  The plastic features of TME rely on  gene regulatory networks based the interplay between transcription factors (TFs), coding and non-coding DNA and chromatin modifications.   In these last years we focused our scientific efforts on TFEB, a basic helix-loop-helix leucine zipper oncogenic TF that participates to cellular adaptation to stressing events, such as, in cancer, the response to therapies or the journey in blood circulation to metastatic dissemination.  TFEB can be expressed both by cancer cells and by TME cells.  Accordingly to these expression patterns, PDAC or melanoma behaviors might be different, opening the perspective of targeting this TF to improve the response to therapies or favorably condition the disease progression.<\/p>\n\n\n\n

<\/span>Research achievements<\/h2>\n\n\n\n

Our projects aim at exploring the mechanisms of tumor dependency on the features of TME and at understanding how such dependency might be modulated by the amount of TFEB expressed in 3 cellular compartments: cancer cells, stroma cells and endothelial cells lining blood capillaries.  We hypothesize that TFEB dosage   changes the structure of the chromatin and influences the role of enhancer thus making groups of genes active or silenced depending on the conditions and theus dynamically influencing cancer-TEM cross-talks<\/p>\n\n\n\n

Our experimental platform entails the deployment of multi-dimensional data (transcriptional, chromatin and enhancer landscapes) obtained in genetic engineered mouse models and in 3D in vitro cellular models recapitulating the circuits between cancer cells and TME. By CRISPR-CAS genome editing, these models allow tunable amount of TFEB in the above mentioned cellular compartments. By this approach, we have demonstrated that: i)  overexpression of TFEB  in PDAC  stellate cells modifies  their differentiation in cancer-associated fibroblasts reducing the desmoplastic  potential of the tumor; ii) TFEB deletion deeply influence the response of vascular capillaries.<\/p>\n\n\n\n

<\/span>Conclusions and perspectives<\/h2>\n\n\n\n

For many years, TFs were considered undruggable. However,  the recent progresses in understanding their molecular features are allowing   the generation of specific inhibitors, with new therapeutic perspective.<\/p>\n\n\n\n

Our studies provide a robust approach to evaluate the role of TFEB dosage in regulating the circuits between cancer and TME cells and to experience the effect of pharmacological TFEB manipulation in the control of cancer progression and response to chemotherapy or targeted therapies. <\/p>\n\n\n\n

<\/span>Publications<\/h2>\n\n\n\n

At this link<\/a><\/strong>, you can find all the scientific publications of the Principal Investigator.<\/p>\n\n\n\t

\n\t\t\n
\n\t
\n\t\t\t\t\t

Selected publications<\/h2>\n\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t\t\t\t\t\tDualVEGFA\/BRAF targeting boosts PD-1 blockade in melanoma through GM-CSF-mediated infiltration of M1 macrophages. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Comunanza V, Gigliotti C, Lamba S, Doronzo G, Vallariello E, Martin V, IsellaC, Medico E, Bardelli A, Sangiolo D, Di Nicolantonio F, Bussolino F. Mol Oncol. 2023 Aug;17(8):1474-1491. doi: 10.1002\/1878-0261.13450. Epub 2023 May 27. PMID: 37183363; PMCID: PMC10399721.\r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tTFEB inhibition induces melanoma shut-down by blocking the cell cycle and rewiring metabolism. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Ariano C, Costanza F, Akman M, Riganti C, Cor\u00e0 D, Casanova E, Astanina E, Comunanza V, Bussolino F, Doronzo G. Cell Death Dis. 2023 May9;14(5):314. doi: 10.1038\/s41419-023-05828-7. PMID: 37160873; PMCID: PMC10170071.\r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tThe TFEB-TGIF1 axis regulates EMT in mouse epicardial cells. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Astanina E, Doronzo G, Cor\u00e0 D, Neri F, Oliviero S, Genova T, Mussano F, Middonti E, Vallariello E, Cencioni C, Valdembri D, Serini G, Limana F, Foglio E, Ballabio A, Bussolino F. Nat Commun. 2022 Sep 3;13(1):5191. doi: 10.1038\/s41467-022-32855-3. PMID: 36057632; PMCID: PMC9440911.\r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tTFEB controls integrin-mediated endothelial cell adhesion by the regulation of cholesterol metabolism. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Ariano C, Riganti C, Cor\u00e0 D, Valdembri D, Mana G, Astanina E, Serini G, Bussolino F, Doronzo G. Angiogenesis. 2022 Nov;25(4):471-492. doi: 10.1007\/s10456-022-09840-x. Epub 2022 May 11. PMID: 35545719; PMCID: PMC9519734.\r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\t\t\t\t\t\t\t\tTFEB controls vascular development by regulating the proliferation of endothelial cells. <\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t

Doronzo G, Astanina E, Cor\u00e0 D, Chiabotto G, Comunanza V, Noghero A, Neri F, Puliafito A, Primo L, Spampanato C, Settembre C, Ballabio A, Camussi G, Oliviero S, Bussolino F. EMBO J. 2019 Feb 1;38(3):e98250. doi: 10.15252\/embj.201798250. Epub 2018 Dec 27. PMID: 30591554; PMCID: PMC6356157.\r\n<\/p>\n\t\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>\n\n\t<\/div>\n","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":true,"footnotes":""},"class_list":["post-1208","laboratory","type-laboratory","status-publish","hentry"],"acf":[],"yoast_head":"\nVASCULAR ONCOLOGY - Istituto di Candiolo<\/title>\n<meta name=\"description\" content=\"Research topic Tumor microenvironment (TME) includes immune and stromal cells, blood vessels, nerves and extracellular matrix.  The Lab is interested\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/\" \/>\n<meta property=\"og:locale\" content=\"it_IT\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"VASCULAR ONCOLOGY - Istituto di Candiolo\" \/>\n<meta property=\"og:description\" content=\"Research topic Tumor microenvironment (TME) includes immune and stromal cells, blood vessels, nerves and extracellular matrix.  The Lab is interested\" \/>\n<meta property=\"og:url\" content=\"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/\" \/>\n<meta property=\"og:site_name\" content=\"Istituto di Candiolo\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/istitutodicandiolo\/\" \/>\n<meta property=\"article:modified_time\" content=\"2025-11-11T17:05:00+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:site\" content=\"@fpoirccs\" \/>\n<meta name=\"twitter:label1\" content=\"Tempo di lettura stimato\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minuti\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/\",\"url\":\"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/\",\"name\":\"VASCULAR ONCOLOGY - Istituto di Candiolo\",\"isPartOf\":{\"@id\":\"https:\/\/irccs.com\/it\/#website\"},\"datePublished\":\"2025-01-25T20:42:45+00:00\",\"dateModified\":\"2025-11-11T17:05:00+00:00\",\"description\":\"Research topic Tumor microenvironment (TME) includes immune and stromal cells, blood vessels, nerves and extracellular matrix.  The Lab is interested\",\"breadcrumb\":{\"@id\":\"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/#breadcrumb\"},\"inLanguage\":\"it-IT\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\/\/irccs.com\/it\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"VASCULAR ONCOLOGY\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/irccs.com\/it\/#website\",\"url\":\"https:\/\/irccs.com\/it\/\",\"name\":\"INOC\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/irccs.com\/it\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"it-IT\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"VASCULAR ONCOLOGY - Istituto di Candiolo","description":"Research topic Tumor microenvironment (TME) includes immune and stromal cells, blood vessels, nerves and extracellular matrix.  The Lab is interested","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/","og_locale":"it_IT","og_type":"article","og_title":"VASCULAR ONCOLOGY - Istituto di Candiolo","og_description":"Research topic Tumor microenvironment (TME) includes immune and stromal cells, blood vessels, nerves and extracellular matrix.  The Lab is interested","og_url":"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/","og_site_name":"Istituto di Candiolo","article_publisher":"https:\/\/www.facebook.com\/istitutodicandiolo\/","article_modified_time":"2025-11-11T17:05:00+00:00","twitter_card":"summary_large_image","twitter_site":"@fpoirccs","twitter_misc":{"Tempo di lettura stimato":"3 minuti"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/","url":"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/","name":"VASCULAR ONCOLOGY - Istituto di Candiolo","isPartOf":{"@id":"https:\/\/irccs.com\/it\/#website"},"datePublished":"2025-01-25T20:42:45+00:00","dateModified":"2025-11-11T17:05:00+00:00","description":"Research topic Tumor microenvironment (TME) includes immune and stromal cells, blood vessels, nerves and extracellular matrix.  The Lab is interested","breadcrumb":{"@id":"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/#breadcrumb"},"inLanguage":"it-IT","potentialAction":[{"@type":"ReadAction","target":["https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/irccs.com\/it\/laboratori\/vascular-oncology\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/irccs.com\/it\/"},{"@type":"ListItem","position":2,"name":"VASCULAR ONCOLOGY"}]},{"@type":"WebSite","@id":"https:\/\/irccs.com\/it\/#website","url":"https:\/\/irccs.com\/it\/","name":"INOC","description":"","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/irccs.com\/it\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"it-IT"}]}},"_links":{"self":[{"href":"https:\/\/irccs.com\/it\/wp-json\/wp\/v2\/laboratory\/1208","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/irccs.com\/it\/wp-json\/wp\/v2\/laboratory"}],"about":[{"href":"https:\/\/irccs.com\/it\/wp-json\/wp\/v2\/types\/laboratory"}],"version-history":[{"count":2,"href":"https:\/\/irccs.com\/it\/wp-json\/wp\/v2\/laboratory\/1208\/revisions"}],"predecessor-version":[{"id":2879,"href":"https:\/\/irccs.com\/it\/wp-json\/wp\/v2\/laboratory\/1208\/revisions\/2879"}],"wp:attachment":[{"href":"https:\/\/irccs.com\/it\/wp-json\/wp\/v2\/media?parent=1208"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}