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Bloccare il tumore agendo sul colesterolo?

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La p53, è conosciuta da circa 40 anni, ed è stata una delle prime proteine la cui versione mutata è stata trovata in moltissime forme tumorali. La versione normale funziona da soppressore della crescita, quella mutata, non riuscendo a svolgere i compiti cui sarebbe preposta, agisce da potenziatore della proliferazione.

Tuttavia non erano ancora ben chiari alcuni suoi comportamenti, e soprattutto le relazioni con la cellula che la ospita.

Ora il gruppo di Giannino Del Sal, docente di Biologia applicata dell’università di Trieste e responsabile del Laboratorio di oncologia molecolare del Laboratorio Nazionale CIB dell’Area Science Park, grazie a un programma finanziato con i fondi del 5 per mille assegnato all’Associazione italiana per la Ricerca sul Cancro (AIRC), ha confermato che, come dimostra un numero crescente di studi degli ultimi anni, lo sviluppo, la proliferazione, la metastatizzazione di un tumore è, anche, una questione di meccanica, e di fisica. E che la p53 mutata, per fare danni, ha bisogno di un certo assetto del tessuto.

Questo dipende dalla catena metabolica del colesterolo, alterando quest’ultima, per esempio con le statine, si può evitare che p53 riesca a fare danni: una scoperta importante, che si è guadagnata le colonne di Nature Cell Biology e che ha già portato a sperimentazioni cliniche.

Spiega Del Sal: “Si è capito che p53 mutata, quando si accumula, dà il via a un processo che si autoalimenta e che rende il tumore aggressivo. Al tempo stesso, però, p53 non riesce ad accumularsi se l’ambiente circostante non è favorevole, se la cellula e il tessuto circostante non hanno un certo livello di tensione, una certa rigidità. Ma queste caratteristiche sono regolate dalla via metabolica del colesterolo: per questo, intervenire su questa via vuol dire inibire tutto il processo che permette a p53 di svolgere il suo ruolo. E questo lo si può fare tanto con le statine quanto, probabilmente, con altri composti, che sono già in sperimentazione clinica”.

Del Sal e i suoi collaboratori sono riusciti a scoprire questi complessi rapporti verificando lo stato genetico e molecolare delle cellule malate, soprattutto di uno dei tumori che ancora oggi più sfuggono al controllo della terapia: quello cosiddetto triplo negativo della mammella, ma anche analizzandone, con microscopi a forza atomica e altre tecniche di morfologia e biomeccanica, tutte le caratteristiche fisiche quali, appunto, la rigidità e la durezza. E la relazione tra la particolare consistenza delle masse tumorali, che i medici conoscono molto bene, e la malignità garantita da p53, è emersa con chiarezza.

“Abbiamo studiato moltissimi composti che potessero agire a questo livello, e ne abbiamo selezionati alcuni molto promettenti, oltre alle statine, a conferma dell’importanza di un approccio traslazionale, che parta dalla conoscenza dei meccanismi alla base del cancro per poi riportare prima possibile quanto scoperto alle necessità del paziente e trovare – questa la speranza – nuove vie terapeutiche”.

L’effetto antitumorale delle statine, pur discusso, è noto da molti anni. Ora, grazie ad AIRC e al lavoro di Del Sal, ha anche una spiegazione biologica.

Fonte: Repubblica Salute

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