{"id":18509,"date":"2021-07-22T11:03:50","date_gmt":"2021-07-22T09:03:50","guid":{"rendered":"https:\/\/idibell.cat\/?p=18509"},"modified":"2021-07-22T11:04:16","modified_gmt":"2021-07-22T09:04:16","slug":"lidibell-i-lico-participen-en-la-troballa-duna-debilitat-que-podria-aprofitar-se-per-tractar-cancers-defectius-per-smarca4","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2021\/07\/lidibell-i-lico-participen-en-la-troballa-duna-debilitat-que-podria-aprofitar-se-per-tractar-cancers-defectius-per-smarca4\/","title":{"rendered":"L\u2019IDIBELL i l\u2019ICO participen en la troballa d\u2019una debilitat que podria aprofitar-se per tractar c\u00e0ncers defectius per SMARCA4"},"content":{"rendered":"

Molts tipus de c\u00e0ncer, com el c\u00e0ncer de pulm\u00f3 o el carcinoma de c\u00e8l\u00b7lules petites d’ovari, tipus hipercalc\u00e8mic (SCCOHT), s\u00f3n portadors de mutacions que inactiven gen\u00e8ticament el gen SMARCA4, un component central del complex remodelador de la cromatina SWI\/SNF, un els principals actors en el control epigen\u00e8tic de l’expressi\u00f3 g\u00e8nica.<\/p>\n

En un estudi publicat recentment a la revista Nature Communications<\/em><\/a>, els investigadors descriuen com la inactivaci\u00f3 de el gen SMARCA4 comporta baixos nivells de KDM6, una fam\u00edlia de desmetiladores d’histones. Aix\u00f2, per si sol, pot explicar per qu\u00e8 aquests tumors escapen de l’activitat anticancer\u00edgena de SAHA, un f\u00e0rmac molt efectiu contra les desacetilases d’histona utilitzat en la medicina de precisi\u00f3. En ser refractaris a aquest f\u00e0rmac, els pacients amb tumors portadors de mutacions que inactivin SMARCA4 es queden sense aquesta opci\u00f3 terap\u00e8utica.<\/p>\n

Els resultats de la recerca mostren que la desregulaci\u00f3 de KDM6 altera la seva funci\u00f3 epigen\u00e8tica i, en els tumors deficients en SMARCA4, les c\u00e8l\u00b7lules es tornen hipersensibles a GSK-J4, un potent inhibidor de desmetilases d’histones. Despr\u00e9s del tractament, nom\u00e9s les c\u00e8l\u00b7lules del tumor activen les seves vies de mort cel\u00b7lular programades -apoptosi o necrosi-, el que comporta a una reducci\u00f3 significativa del tumor, tant in vitro com en models animals. De confirmar-se en proves amb pacients humans, s’obriria la porta a nous tractaments per a tumors sense opci\u00f3 terap\u00e8utica espec\u00edfica.<\/p>\n

Els seus resultats es van validar mitjan\u00e7ant l’\u00fas de models de ratolins ortot\u00f2pics que porten un tumor primari hum\u00e0 derivat directament de pacients, els anomenats orthoxenografts, per provar el potencial terap\u00e8utic dels inhibidors de KDM6 en un context fisiol\u00f2gic real. Tots els experiments amb animals van ser aprovats pel Comit\u00e8 d’\u00c8tica de l’IDIBELL.<\/p>\n

Estudi col\u00b7laboratiu multic\u00e8ntric<\/strong><\/p>\n

En aquest estudi hi han participat investigadors\/es de l\u2019Institut Josep Carreras, l\u2019ICO, l\u2019IDIBELL, el VHIO i la Universitat de Granada. Concretament, per part de l\u2019IDIBELL ho ha coordinat l\u2019 Alberto Villanueva, cap del grup de Quimioresist\u00e8ncia Tumoral i Estromal<\/a> del Programa Procure de l\u2019IDIBELL i de l\u2019ICO, amb la col\u00b7laboraci\u00f3 de Lourdes Farr\u00e9, Agust\u00ed Vidal i Maties Guiu, del Servei d\u2019Anatomia Patol\u00f2gica, i l\u2019onc\u00f2leg m\u00e8dic de l\u2019IDIBELL i de l\u2019ICO l\u2019Hospitalet, Josep Ma Piulats.<\/p>\n

Els resultats reportats poden ser de gran valor per a l’estratificaci\u00f3 de tumors segons el seu origen gen\u00e8tic o epigen\u00e8tic i fomentar el desenvolupament de la medicina de precisi\u00f3 amb alta efic\u00e0cia i baixa toxicitat, utilitzant un nou conjunt de moduladors epigen\u00e8tics com a f\u00e0rmacs anticancerosos molt \u00fatils per al futur tractament de c\u00e0ncers de pulm\u00f3 i altres c\u00e0ncers epitelials, com els tumors d’ovari.<\/p>\n

 <\/p>\n

 <\/p>\n

L\u2019Institut d’Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL) \u00e9s un centre de recerca en biomedicina creat l\u2019any 2004. Est\u00e0 participat per l’Hospital Universitari de Bellvitge i l\u2019Hospital de Viladecans de l’Institut Catal\u00e0 de la Salut, l’Institut Catal\u00e0 d’Oncologia, la Universitat de Barcelona i l\u2019Ajuntament de l\u2019Hospitalet de Llobregat.<\/em><\/p>\n

L\u2019IDIBELL \u00e9s membre del Campus d’Excel\u00b7l\u00e8ncia Internacional de la Universitat de Barcelona HUBc i forma part de la instituci\u00f3 CERCA de la Generalitat de Catalunya. L’any 2009 es va convertir en un dels cinc primers centres d\u2019investigaci\u00f3 espanyols acreditats com a institut d\u2019investigaci\u00f3 sanit\u00e0ria per l\u2019Instituto de Salud Carlos III. A m\u00e9s, forma part del programa \u201cHR Excellence in Research\u201d de la Uni\u00f3 Europea i \u00e9s membre de EATRIS i REGIC. Des de l\u2019any 2018, l\u2019IDIBELL \u00e9s un Centro Acreditado de la Fundaci\u00f3n Cient\u00edfica AECC (FCAECC).<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Els resultats de l\u2019estudi apunten que els tumors amb una forma gen\u00e8ticament inactivada de la prote\u00efna remodeladora de la cromatina SMARCA4 s\u00f3n molt sensibles als inhibidors de la fam\u00edlia de desmetiladores d’histones KDM6.<\/p>\n","protected":false},"author":8,"featured_media":18511,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[332,447,452,346],"tags":[],"class_list":["post-18509","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cancer","category-p-de-mecanismes-molelculars-i-terapia-experimental-en-oncologia-oncobell","category-procure","category-quimioresistencia-tumoral-i-estromal"],"publishpress_future_action":{"enabled":false,"date":"2025-01-29 05:18:49","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/18509","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=18509"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/18509\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/18511"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=18509"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=18509"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=18509"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}