Il cancro al fegato ha dimostrato di avere la capacità di modificare il proprio metabolismo per sfuggire ai trattamenti farmacologici. Questo fenomeno è emerso da uno studio condotto dall’Università Statale di Milano e dall’Istituto Europeo di Oncologia (IEO), supportato dalla Fondazione AIRC, e pubblicato sulla rivista “Signal Transduction and Targeted Therapy” del gruppo Nature. La ricerca, datata 27 giugno 2025, ha rivelato che le cellule tumorali del fegato possono subire cambiamenti metabolici significativi, rendendole resistenti alle terapie.
Il meccanismo di resistenza delle cellule tumorali
I ricercatori hanno esaminato il comportamento delle cellule tumorali in colture cellulari sottoposte a trattamento con sorafenib, un farmaco utilizzato nelle fasi avanzate del carcinoma epatocellulare, una delle forme più diffuse di cancro al fegato. Nonostante l’iniziale efficacia del sorafenib, circa il 50% dei pazienti sviluppa resistenza al farmaco dopo alcuni mesi di terapia. Gli scienziati hanno scoperto che le cellule tumorali riescono a deviare le vie metaboliche degli zuccheri per produrre glicerolo, una molecola fondamentale per la costruzione di nuove membrane cellulari. Questo processo avviene in concomitanza con l’assorbimento di acidi grassi dall’ambiente esterno, che si legano al glicerolo, permettendo così la creazione di una nuova struttura membranosa. Tale rimodellamento conferisce alle cellule tumorali una maggiore resistenza agli stress indotti dai trattamenti.
Implicazioni per la diagnosi e il trattamento
Nico Mitro, docente di Biochimica all’Università Statale di Milano e già vincitore del Career Development Award della Fondazione Armenise-Harvard, ha spiegato che le cellule tumorali, similmente ad alcuni animali che cambiano pelle per adattarsi, modificano la loro struttura per sfuggire agli effetti dei farmaci. Durante il trattamento, le cellule sopravvissute riescono a riorganizzare i lipidi nella loro membrana esterna, aumentando così la loro resistenza. Uno degli aspetti più promettenti identificati nello studio è l’individuazione di due possibili biomarcatori nel sangue dei pazienti trattati con sorafenib. L’accumulo di D-lattato potrebbe indicare l’efficacia del trattamento, mentre un aumento di glicerolo potrebbe segnalare l’insorgenza della resistenza tumorale. Questi biomarcatori potrebbero diventare strumenti preziosi per monitorare l’efficacia delle terapie e per intervenire con strategie alternative tempestive.
Prospettive future nella lotta contro il carcinoma epatocellulare
Le scoperte di questo studio aprono nuove strade nella lotta contro il carcinoma epatocellulare e nella comprensione dei meccanismi di resistenza ai farmaci. Mitro ha sottolineato che una conoscenza più approfondita dei processi metabolici delle cellule tumorali potrebbe portare allo sviluppo di terapie sempre più mirate e capaci di migliorare l’efficacia dei trattamenti e la qualità della vita dei pazienti. La ricerca è stata coordinata da Mitro e ha coinvolto scienziati del Dipartimento di Scienze Farmacologiche e Biomolecolari dell’Università degli Studi di Milano e del Dipartimento di Oncologia Sperimentale dell’IEO. Hanno partecipato anche altri centri italiani, tra cui l’IRCCS Istituto Romagnolo per lo Studio dei Tumori di Meldola e l’IRCCS Ospedale San Raffaele di Milano.
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