{"id":125218,"date":"2025-04-09T15:54:01","date_gmt":"2025-04-09T13:54:01","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=125218"},"modified":"2025-04-09T16:24:05","modified_gmt":"2025-04-09T14:24:05","slug":"new-advances-in-the-fight-against-the-most-common-form-of-lung-cancer","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/nous-avencos-en-la-lluita-contra-el-cancer-de-pulmo-mes-frequent","title":{"rendered":"Nous aven\u00e7os en la lluita contra el c\u00e0ncer de pulm\u00f3 m\u00e9s freq\u00fcent"},"content":{"rendered":"\n

Un estudi liderat per la Universitat de Barcelona en col\u00b7laboraci\u00f3 amb l’Institut de Bioenginyeria de Catalunya revela que l’assaig funcional\u00a0dynamic BH3 profiling\u00a0(DBP) \u00e9s capa\u00e7 de predir si tractaments espec\u00edfics seran efectius en aquests pacients de c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lules no petites. La t\u00e8cnica ajuda a determinar quina ter\u00e0pia ser\u00e0 m\u00e9s efica\u00e7 provant-ho directament en c\u00e8l\u00b7lules vives, tot millorant les ter\u00e0pies personalitzades.<\/strong><\/p>\n\n\n\n

\"\"
De dreta a esquerra, Fernando Mart\u00edn and Joan Montero at the Faculty of Medicine and Health Sciences. \/ Cr\u00e8dit: Universitat de Barcelona<\/figcaption><\/figure>\n\n\n\n

Un 85\u00a0% dels casos diagnosticats de c\u00e0ncer de pulm\u00f3 s\u00f3n del tipus de c\u00e8l\u00b7lules no petites (NSCLC, per les sigles en angl\u00e8s). En aquest grup, el 5\u00a0% dels pacients mostren alteracions moleculars en el gen\u00a0ALK<\/em>, que est\u00e0 implicat en la multiplicaci\u00f3 cel\u00b7lular. L\u2019\u00fas d\u2019inhibidors contra aquest oncog\u00e8n \u2014una de les estrat\u00e8gies m\u00e9s efectives contra aquest tipus de c\u00e0ncer\u2014 ha beneficiat molts pacients. Per\u00f2 hi ha manera de saber si el tractament ser\u00e0 efectiu en totes les persones afectades?<\/p>\n\n\n\n

Ara, un estudi liderat per la Universitat de Barcelona revela que l\u2019assaig funcional dynamic BH3 profiling <\/em>(DBP) \u00e9s capa\u00e7 de predir si aquest tractament ser\u00e0 efectiu en aquests pacients oncol\u00f2gics i millorar, aix\u00ed, les ter\u00e0pies personalitzades. Aquesta t\u00e8cnica assoleix amb tumors una cosa molt semblant al que aconsegueix un antibiograma amb una infecci\u00f3 bacteriana: determinar quina ter\u00e0pia ser\u00e0 m\u00e9s efica\u00e7 provant-lo directament en c\u00e8l\u00b7lules vives.<\/p>\n\n\n\n

La t\u00e8cnica, que ajuda a seleccionar el millor f\u00e0rmac per a cada pacient, la va patentar l\u2019any 2015 el Dana-Farber Cancer Institute (Boston, Estats Units) i el seu coinventor \u00e9s Joan Montero, professor de la Facultat de Medicina i Ci\u00e8ncies de la Salut de la UB i de l\u2019\u00e0rea de Bioenginyeria, Biomaterials i Nanomedicina del Centre de Recerca Biom\u00e8dica en Xarxa (CIBERBBN).<\/p>\n\n\n\n

El nou estudi, publicat a la revista Cell Death and Disease<\/em><\/a>, del grup Nature, el dirigeix el professor Montero i t\u00e9 com a primer autor l\u2019investigador Fernando Mart\u00edn, membre de la UB, l\u2019Institut de Bioenginyeria de Catalunya (IBEC) i el CIBERBBN. En el treball tamb\u00e9 hi col\u00b7laboren equips de la Facultat de F\u00edsica de la UB, l\u2019Hospital Cl\u00ednic, l\u2019Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) i l\u2019Institut Catal\u00e0 d\u2019Oncologia (ICO).<\/p>\n\n\n\n

La recerca, duta a terme amb models animals i bi\u00f2psies de pacients, revela tamb\u00e9 per primera vegada que la prote\u00efna MCL-1 t\u00e9 un rol fonamental en la resist\u00e8ncia dels tumors davant d\u2019aquest tipus de ter\u00e0pies. A m\u00e9s, constata que les mol\u00e8cules conegudes com a BH3 mimetics<\/em> poden millorar l\u2019efecte dels tractaments oncol\u00f2gics en evitar les adaptacions tumorals davant els inhibidors de la prote\u00efna-cinasa del limfoma anapl\u00e0stic (ALK), un dels principals tractaments contra aquest c\u00e0ncer.<\/p>\n\n\n\n

Predir la resposta dels f\u00e0rmacs contra el c\u00e0ncer de pulm\u00f3 m\u00e9s freq\u00fcent<\/strong><\/strong><\/h4>\n\n\n\n

Cada tumor \u00e9s \u00fanic, i predir la resposta terap\u00e8utica contra el c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lules no petites suposa un gran aven\u00e7 en la medicina personalitzada. Davant d\u2019aquest desafiament en biomedicina, l\u2019estudi confirma que la t\u00e8cnica dynamic BH3 profiling<\/em> t\u00e9 una excel\u00b7lent capacitat predictiva de la resposta de les c\u00e8l\u00b7lules tumorals davant els inhibidors d\u2019ALK.<\/p>\n\n\n\n

Els inhibidors d\u2019ALK s\u2019utilitzen a l\u2019inici de la malaltia en pacients de c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lules no petites que mostren alteracions moleculars en aquest oncog\u00e8n. Actualment, s\u2019han desenvolupat quatre generacions d\u2019inhibidors d\u2019ALK amb una efic\u00e0cia cl\u00ednica superior a la quimioter\u00e0pia.<\/p>\n\n\n\n

\u00abAquestes ter\u00e0pies dirigides s\u00f3n les que confereixen una superviv\u00e8ncia m\u00e9s gran en c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lules no petites i es toleren millor que els agents citot\u00f2xics. L\u2019\u00fas d\u2019inhibidors d\u2019ALK en la cl\u00ednica no nom\u00e9s incrementa la superviv\u00e8ncia dels pacients, sin\u00f3 que tamb\u00e9 en millora la qualitat de vida\u00bb, detalla el professor Joan Montero, del Departament de Biomedicina de la UB.<\/p>\n\n\n\n

\n

Aquestes ter\u00e0pies dirigides s\u00f3n les que confereixen una superviv\u00e8ncia m\u00e9s gran en c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lules no petites i es toleren millor que els agents citot\u00f2xics. L\u2019\u00fas d\u2019inhibidors d\u2019ALK en la cl\u00ednica no nom\u00e9s incrementa la superviv\u00e8ncia dels pacients, sin\u00f3 que tamb\u00e9 en millora la qualitat de vida<\/p>\n\n\n\n

Joan Montero<\/p>\n<\/blockquote>\n\n\n\n

\u00abEn aquest context, la t\u00e8cnica\u00a0dynamic BH3 profiling\u00a0<\/em>podria complementar l\u2019aplicaci\u00f3 dels assajos gen\u00f2mics i la seq\u00fcenciaci\u00f3 massiva que guien de manera rutin\u00e0ria l\u2019\u00fas d\u2019aquestes ter\u00e0pies dirigides als pacients oncol\u00f2gics, i, especialment, en casos complexos\u00bb, explica el professor.<\/p>\n\n\n\n

Com actuen els inhibidors d\u2019ALK en el c\u00e0ncer?<\/strong><\/strong><\/h4>\n\n\n\n

En els pacients de c\u00e0ncer de tipus NSCLC, es produeix la fusi\u00f3 de dos gens \u2014ALK<\/em> i el gen EML4 <\/em>en el 90 % dels casos\u2014 que origina un nou gen capa\u00e7 de codificar una prote\u00efna mutada i activar les vies de senyalitzaci\u00f3 que promouen la proliferaci\u00f3 tumoral. \u00abEn la seva acci\u00f3 terap\u00e8utica, els inhibidors d\u2019ALK s\u2019uneixen espec\u00edficament en el lloc actiu de la prote\u00efna quimera i n\u2019impedeixen l\u2019activitat cinasa. D\u2019aquesta manera, aquests f\u00e0rmacs inhibeixen la fosforilaci\u00f3 i activaci\u00f3 d\u2019altres prote\u00efnes diana involucrades en el creixement i la superviv\u00e8ncia de les c\u00e8l\u00b7lules tumorals\u00bb, indica Fernando Mart\u00edn.<\/p>\n\n\n\n

A difer\u00e8ncia de molts agents quimioterap\u00e8utics, \u00abels inhibidors d\u2019ALK poden travessar la barrera hematoencef\u00e0lica i arribar al sistema nervi\u00f3s central\u00bb. \u00abCom que un ter\u00e7 dels pacients amb c\u00e0ncer NSCLC en fases avan\u00e7ades presenten met\u00e0stasi al cervell, aquesta capacitat resulta especialment beneficiosa en la lluita contra els tumors. Aquest tipus de ter\u00e0pia tamb\u00e9 \u00e9s aplicable en el limfoma anapl\u00e0stic de c\u00e8l\u00b7lules grans o el neuroblastoma\u00bb, apunta l\u2019investigador.<\/p>\n\n\n\n

\"From
De dreta a esquerra, Paula Morales, Clara Alcon, Fernando Mart\u00edn, Joan Montero, Albert Manzano i Marina Bantul\u00e0. \/Cr\u00e8dit: Universitat de Barcelona<\/figcaption><\/figure>\n\n\n\n

C\u00e8l\u00b7lules tumorals que s\u2019escapen de la mort per apoptosi<\/strong><\/h4>\n\n\n\n

Malgrat els aven\u00e7os en el tractament, la resposta terap\u00e8utica als inhibidors d\u2019ALK no \u00e9s sempre duradora. Les c\u00e8l\u00b7lules canceroses que encara persisteixen s\u00f3n resistents a la mort per apoptosi (mort cel\u00b7lular programada) i les opcions de tractament contra la resist\u00e8ncia cel\u00b7lular s\u00f3n limitades.<\/p>\n\n\n\n

L\u2019estudi descriu per primera vegada que la prote\u00efna antiapopt\u00f2tica MCL-1 tamb\u00e9 t\u00e9 un rol fonamental en la resist\u00e8ncia enfront d\u2019aquestes ter\u00e0pies. \u00abUna de les caracter\u00edstiques principals de les c\u00e8l\u00b7lules resistents a la ter\u00e0pia \u00e9s la capacitat per evitar la mort cel\u00b7lular apopt\u00f2tica, un mecanisme cel\u00b7lular regulat per la fam\u00edlia de prote\u00efnes BCL-2. El balan\u00e7 entre els components proapopt\u00f2tics i antiapopt\u00f2tics regula finalment la resist\u00e8ncia a la mort cel\u00b7lular i l\u2019adaptaci\u00f3 a la ter\u00e0pia\u00bb, detallen els investigadors.<\/p>\n\n\n\n

En estudis anteriors, els autors van descriure com les prote\u00efnes antiapopt\u00f2tiques de la fam\u00edlia BCL-2 poden protegir les c\u00e8l\u00b7lules de c\u00e0ncer de pulm\u00f3 davant ter\u00e0pies dirigides contra oncogens com KRAS o EGFR. No obstant aix\u00f2, es desconeixia el paper d\u2019aquesta fam\u00edlia en la resist\u00e8ncia enfront d\u2019inhibidors d\u2019ALK.<\/p>\n\n\n\n

A m\u00e9s, la t\u00e8cnica dynamic BH3 profiling<\/em> tamb\u00e9 permet desxifrar les adaptacions antiapopt\u00f2tiques que sorgeixen en resposta a inhibidors d\u2019ALK. \u00abAquestes adaptacions agudes es poden prevenir amb l\u2019\u00fas de BH3 mimetics<\/em> (petites mol\u00e8cules que inhibeixen amb una elevada especificitat prote\u00efnes antiapopt\u00f2tiques) per millorar l\u2019efecte del tractament in vitro<\/em> i in vivo<\/em>\u00bb, apunten els experts.<\/p>\n\n\n\n

\u00abPer exemple, el f\u00e0rmac Venetoclax \u2014un inhibidor de la prote\u00efna antiapopt\u00f2tica BCL-2\u2014 s\u2019ha aprovat amb \u00e8xit per a \u00fas cl\u00ednic. En paral\u00b7lel, alguns inhibidors d\u2019altres prote\u00efnes antiapopt\u00f2tiques com MCL-1 estan sent avaluats en assajos cl\u00ednics\u00bb, continuen. \u00abEl nostre treball tamb\u00e9 proposa alternatives a l\u2019\u00fas de BH3 mimetics<\/em> per inhibir de manera indirecta per\u00f2 efectiva aquestes prote\u00efnes i millorar substancialment l\u2019efecte dels inhibidors d\u2019ALK\u00bb.<\/p>\n\n\n\n

Entre els projectes de futur m\u00e9s immediats, l\u2019equip impulsar\u00e0 noves recerques per determinar si aquestes resist\u00e8ncies antiapopt\u00f2tiques es poden manifestar durant per\u00edodes m\u00e9s llargs d\u2019exposici\u00f3 al f\u00e0rmac (per exemple, en la senesc\u00e8ncia indu\u00efda per ter\u00e0pia). \u00abTamb\u00e9 seria molt rellevant desxifrar quina proporci\u00f3 de pacients podria beneficiar-se de l\u2019ocupaci\u00f3 de la t\u00e8cnica dynamic BH3 profiling<\/em>, i de la combinaci\u00f3 amb BH3 mimetics<\/em> i altres f\u00e0rmacs contra prote\u00efnes antiapopt\u00f2tiques\u00bb, conclouen Joan Montero i Fernando Mart\u00edn.<\/p>\n\n\n\n

\n\n\n\n

Article de refer\u00e8ncia:<\/strong><\/strong><\/p>\n\n\n\n

Mart\u00edn, Fernando; Alcon, Clara; Mar\u00edn, Elba; Morales-S\u00e1nchez, Paula; Manzano-Mu\u00f1oz, Albert; D\u00edaz, Sherley; Garc\u00eda, Mireia; Samitier, Josep; Lu, Albert; Villanueva, Alberto; Reguart, Noem\u00ed; Teixid\u00f3, Cristina; Montero, Joan. \u00abNovel selective strategies targeting the BCL-2 family to enhance clinical efficacy in ALK-rearranged non-small cell lung cancer\u00bb<\/a>. Cell Death and Disease<\/em>, marzo de 2025. DOI: 10.1038\/s41419-025-07513-3<\/p>\n\n\n\n

\n\n\n\n

Via University of Barcelona<\/a><\/p>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Un estudi liderat per la Universitat de Barcelona en col\u00b7laboraci\u00f3 amb l’Institut de Bioenginyeria de Catalunya revela que l’assaig funcional\u00a0dynamic BH3 profiling\u00a0(DBP) \u00e9s capa\u00e7 de predir si tractaments espec\u00edfics seran efectius en aquests pacients de c\u00e0ncer de pulm\u00f3 de c\u00e8l\u00b7lules no petites. 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