S\u2019obre una porta a una nova ter\u00e0pia combinada per tractar els c\u00e0ncers de pr\u00f2stata m\u00e9s agressius i resistents. Aquesta \u00e9s una de les conclusions a les quals han arribat investigadors de l\u2019Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), liderats pel Dr. \u00c1lvaro Ayt\u00e9s. L\u2019equip de treball, que acaba de publicar els seus darrers resultats a la revista Nature Communications, inclou, tamb\u00e9, investigadors de l\u2019Institut Catal\u00e0 d\u2019Oncologia, de la Universitat de Columbia a Nova York i de la Universitat de Berna a Su\u00efssa.<\/p>\n
\u00a0<\/p>\n
L\u2019estudi ha identificat una nova vulnerabilitat a la qual atacar en els c\u00e0ncers de pr\u00f2stata m\u00e9s agressius, metast\u00e0tics i que s\u2019han fet resistents a les ter\u00e0pies hormonals disponibles a dia d\u2019avui. En concret, els investigadors han demostrat que aquests tumors generen nivells creixents de la prote\u00efna NSD2 a mida que avan\u00e7a la progressi\u00f3 tumoral i l\u2019adquisici\u00f3 de resist\u00e8ncia a les ter\u00e0pies. A m\u00e9s, han pogut validar experimentalment que aquests tumors, per a seguir creixent i disseminant-se, s\u00f3n dependents d\u2019aquesta prote\u00efna. Per aquests motius, NSD2 representa una diana terap\u00e8utica emergent contra la qual dirigir nous tractaments.<\/p>\n
\u00a0<\/p>\n
Per arribar a aquests resultats, els investigadors han utilitzat un seguit de l\u00ednies de ratolins transg\u00e8nics portadors de mutacions prevalents en els pacients de c\u00e0ncer de pr\u00f2stata. Aquestes mutacions s\u00f3n nom\u00e9s actives en les c\u00e8l\u00b7lules de l\u2019epiteli prost\u00e0tic dels ratolins, tal com ocorre en la gran majoria de pacients. Partint d\u2019aquests models, un cop els ratolins han desenvolupat c\u00e0ncer, s\u2019han a\u00efllat c\u00e8l\u00b7lules tant dels tumors primaris de pr\u00f2stata com de les met\u00e0stasis i se n\u2019han analitzat els patrons d\u2019expressi\u00f3 g\u00e8nica. Mitjan\u00e7ant l\u2019\u00fas d\u2019eines bioinform\u00e0tiques, els investigadors han identificat gens candidats a representar una vulnerabilitat en aquests tumors tan agressius. Gr\u00e0cies a aquesta aproximaci\u00f3 experimental, s\u2019han identificat els factors que, de forma diferencial, estan presents en la malignitzaci\u00f3 i la met\u00e0stasi. NSD2 n\u2019\u00e9s un dels principals exponents.<\/p>\n
\u00a0<\/p>\n
La NSD2 \u00e9s una prote\u00efna amb activitat enzim\u00e0tica que introdueix modificacions qu\u00edmiques (en concret, grups metil) a les prote\u00efnes que donen suport estructural als filaments d\u2019ADN, anomenades histones. Aquest proc\u00e9s de modificaci\u00f3 qu\u00edmica de l\u2019ADN, o epigen\u00e8tica, sovint s\u2019associa al control, temporal i en els diferents teixits, de l\u2019expressi\u00f3 g\u00e8nica. En concret, les modificacions en aquestes histones produ\u00efdes per l\u2019acci\u00f3 d\u2019NSD2 donen lloc a una relaxaci\u00f3 en els nivells de compactaci\u00f3 dels filaments d\u2019ADN (coneguts amb el nom de cromatina), desencadenant l\u2019activaci\u00f3 de l\u2019expressi\u00f3 d\u2019un conjunt de gens amb potencial tumorig\u00e8nic.<\/p>\n
\u00a0<\/p>\n
Una de les principals hip\u00f2tesis dels investigadors que signen aquest estudi \u00e9s que l\u2019activaci\u00f3 d\u2019aquests gens com a resultat de l\u2019acci\u00f3 d\u2019NSD2 \u00e9s la responsable de la resist\u00e8ncia als tractaments quimioter\u00e0pics que, de forma habitual, s\u2019administren als pacients de c\u00e0ncer de pr\u00f2stata. En aquest sentit, els investigadors treballen amb mol\u00e8cules que puguin inhibir la funci\u00f3 d\u2019NSD2 i, per tant, disminuir la malignitat dels tumors de pr\u00f2stata en ratolins. En efecte, l\u2019estudi ha demostrat que la inhibici\u00f3 farmacol\u00f2gica d\u2019NSD2 es tradueix en un augment de la superviv\u00e8ncia del model experimental, una disminuci\u00f3 de les met\u00e0stasis i una reducci\u00f3 de la mida dels tumors.<\/p>\n
Gr\u00e0cies a aquests resultats, els investigadors conclouen que la inhibici\u00f3 d\u2019NSD2 podria conduir a re-sensibilitzar els tumors de pr\u00f2stata que presenten resist\u00e8ncia als tractaments antiandrog\u00e8nics habituals. Aquest fet obre una prometedora porta a la implementaci\u00f3 d\u2019una ter\u00e0pia combinada que inclouria l\u2019administraci\u00f3 d\u2019un f\u00e0rmac inhibidor d\u2019NSD2 conjuntament amb els f\u00e0rmacs antiandrog\u00e8nics convencionals.<\/p>\n","protected":false},"excerpt":{"rendered":"
Investigadors de l\u2019IDIBELL i de l\u2019ICO han demostrat que els tumors de pr\u00f2stata m\u00e9s agressius generen nivells creixents de la prote\u00efna NSD2 a mida que avan\u00e7a la progressi\u00f3 tumoral i l\u2019adquisici\u00f3 de resist\u00e8ncia a les ter\u00e0pies<\/p>\n","protected":false},"author":6,"featured_media":10519,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","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":[332,395],"tags":[],"class_list":["post-7534","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cancer","category-mecanismes-de-resistencia-i-progressio-en-el-cancer-de-prostata"],"publishpress_future_action":{"enabled":false,"date":"2024-10-24 20:43:30","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/7534"}],"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\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=7534"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/7534\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/10519"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=7534"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=7534"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=7534"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}