Event

Tumor heterogeneity in colon cancer: therapeutic implications

Il 31/05/2017 ore 14.30 - 15.30

Aula Conferenze CNR, Via P. Castellino,111 80131 Napoli

Dr Nicola Normanno from the Istituto Nazionale Tumori 'Fondazione G. Pascale'-Ircss, Naples, will give a seminar on the molecular heterogeneity of colon cancer.

The epidermal growth factor receptor (EGFR) and its ligands play a relevant role in the pathogenesis and progression of colorectal carcinoma (CRC). Anti-EGFR monoclonal antibodies have been approved for the treatment of patients with metastatic CRC. However, a number of genetic alterations have been hypothesized to cause de novo and acquired resistance to EGFR monoclonal antibodies. By using next generation sequencing (NGS)-based techniques, we have described the molecular heterogeneity of CRC within a clinical trial aiming to explore the activity of the anti-EGFR monoclonal antibodies cetuximab beyond progression in metastatic CRC patients (the CAPRI trial). Among patients receiving first-line cetuximab plus FOLFIRI, those without mutations in KRAS, NRAS, BRAF or PIK3CA (i.e. quadruple wild type) showed an higher response rate and a longer progression free survival as compared with patients carrying variants in any of the four genes. We also found that the majority of CRC carry different driver mutations, with some tumors showing a complex mutational profile. Although most of driver mutations were likely to be clonal, some tumors were found to carry sub-clonal KRAS, NRAS, BRAF or PIK3CA variants. Importantly, the presence of sub-clonal KRAS mutations was associated with resistance to anti-EGFR agents. Finally, treatment beyond progression with cetuximab plus chemotherapy (FOLFOX) resulted in a longer progression free survival as compared with chemotherapy alone among patients with quadruple wild type tumors. In conclusion, mutational profiling with NGS allows to recapitulate the inter- and intra-tumor heterogeneity of CRC and to identify subgroups of patients with high sensitivity to anti-EGFR agents.

Organizzato da:
Ibp-Cnr

Referente organizzativo:
Alberto Luini
Cnr - Istituto di biochimica delle proteine
Via P. Castellino,111 80131 Napoli
a.luini@ibp.cnr.it
081/6132722

Modalità di accesso: ingresso libero