Da un farmaco antipsicotico nuove speranze contro il tumore al pancreas. Importante studio condotto dal Cnr-Nanotec di Rende in collaborazione con l’Unical

Il cancro al pancreas è uno dei tumori più letali e i farmaci finora a disposizione per combatterlo sono solo i generici trattamenti chemioterapici.

Il coinvolgimento in questa patologia della proteina Nupr1, appartenente alla classe speciale delle «proteine intrinsecamente disordinate», è stato dimostrato fin dagli anni Novanta da un’équipe dell’Istituto nazionale della sanità di Marsiglia.

L’obiettivo di individuare una molecola in grado di inibire questa proteina è stato ora raggiunto grazie a uno studio condotto dall’Istituto di nanotecnologia del Consiglio nazionale delle ricerche (Cnr-Nanotec) di Rende (Cosenza), in collaborazione con l’Università della Calabria e varie unità di ricerca spagnole, tra cui le Università di Elche e di Saragozza, il Centro di malattie epatodigestive di Madrid e il Cancer Center di Marsiglia.

«La ricerca è cominciata con lo screening di oltre mille farmaci già approvati per varie indicazioni terapeutiche», spiega Bruno Rizzuti del Cnr-Nanotec di Rende.

«L’uso combinato di tecniche sperimentali e di simulazioni al calcolatore ha permesso di identificare alcuni di questi farmaci in grado di interagire con la proteina Nupr1. Esperimenti ‘in vitro’ hanno poi dimostrato che i composti selezionati sono capaci di diminuire la vitalità delle cellule tumorali, di ridurne le capacità di migrazione e di sopprimere completamente la possibilità di formazione di colonie.

«Il composto più efficace», spiega il dottore Rizzuti «una molecola nota come trifluoperazina, finora utilizzata solo per la sua azione antipsicotica, è stato sperimentato in vivo su cellule del tumore del pancreas umano trapiantate su modelli murini, e si è dimostrato in grado di arrestare completamente lo sviluppo della malattia.

«La molecola in questione ha avvalorato un’efficacia antitumorale superiore perfino ai più potenti trattamenti chemioterapici finora disponibili. Inoltre, lo studio prova che questa nuova molecola non costituirebbe solo un’alternativa ai farmaci già noti, ma può essere combinata con questi per aumentare l’effetto terapeutico complessivo».

Al di là delle possibili ricadute mediche future, e in attesa che si avvii la sperimentazione per l’uso di questo farmaco sull’uomo, questo lavoro segna un passo importante nella ricerca sulle «proteine con struttura disordinata».

«Secondo uno dei dogmi della biologia classica», aggiunge il ricercatore del Cnr-Nanotec di Rende, «la conformazione di una proteina dovrebbe essere unica e ben definita per consentire a ciascuna di queste “macchine molecolari” di svolgere una precisa funzione. Le “proteine disordinate” rovesciano la validità di questo principio e, grazie alla loro struttura flessibile, sono in grado di svolgere molteplici funzioni di comunicazione e regolazione cellulare.

«Tuttavia, quest’assenza di elementi strutturali ben definiti appariva in passato un ostacolo invalicabile per procedere al design razionale di farmaci selettivi per contrastarne l’azione.

«La dimostrazione della possibilità di individuare molecole attive in grado di inibire le “proteine disordinate” è un importante passo in avanti che cambia completamente lo scenario nella lotta a numerose patologie e apre la possibilità di moltiplicare il numero di bersagli molecolari che si possono colpire attraverso l’uso mirato di farmaci».

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