• Simona De Summa, Katia Danza, Brunella Pilato, Giuseppina Matera, Rossella Fasano, Angela Calabrese, Rosanna Lacalamita, Nicola Silvestris, Stefania Tommasi, Antonella Argentiero, and Oronzo Brunetti.
• Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
• Medicina (Kaunas). 2021 Nov 13; 57 (11).

AbstractColorectal cancer (CRC) is one of the most common cancer types around the world. The prognosis of patients with advanced diseases is still poor in spite of currently available therapeutic options. Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved to treat refractory metastatic colorectal cancer (mCRC). We investigated Somatic mutations in several genes involved in immunological response and cancer progression in both long/short responder mCRC patients who underwent third-line therapy with regorafenib to identify predictive biomarkers of response using Ion Torrent PGM sequencing and bioinformatic tools. We found Somatic mutations in TGFBR1, TGFBR2, and TGFBR3 genes in primary tumor and metastases samples of long-responder patients. Furthermore, our bioinformatic results show that they were mainly enriched in immune response, cell junction, and cell adhesion in long responder patients, particularly in primary tumor and metastatic sites. These data suggest that the TGF-b pattern could be the leading actor of a prolonged response to this drug.

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