Translational Research

In addition to its clinical activities, the GI Group has started an exhaustive program of translational research (TR) based mainly on the PETACC2, PETACC3 and EPOC trials. It has established an international network of pathologists and laboratories with decentralized tissue processing. Interaction with the EORTC virtual tumor bank has been developed so that it can function as backbone for this collaborative research.

The tumoral material from the PETACC-3 protocol, a phase III randomized trial of adjuvant chemotherapy in colon cancer, has been analyzed in terms of several markers including MSI, KRAS, BRAF,SMAD4, TS, 18qLOH, and p53. This work allowed the investigation of the prognostic value of KRAS and BRAF according to the MSI status of the tumors in a large homogeneous patient population.

For the PETACC-2 TR project, tissue microarrays have been prepared on 650 cases, DNA extraction has been performed on 300 cases, 300 slides have been sent to the virtual tumor bank, and RNA analyses have also been launched. TR analyses are ongoing.

Histopathological analysis was performed on the tissue from liver metastases of CRC in the EPOC protocol.

The ongoing PETACC-8 trial also includes an ambitious TR program including DNA analysis for LOH, mitochondrial mutations, SNP of metabolizing enzymes, and establishes tissue arrays for analysis of EGF-R homo- and hetero-dimer formation.

The GI Group is developing a TR program for the EndoTAG trial proposal (EORTC 40093), a phase III trial of EndoTAG-1 plus gemcitabine versus gemcitabine alone in patients with unresectable locally advanced/ metastatic adenocarcinoma of the pancreas. EndoTAG-1 represents a promising candidate for the treatment of solid malignancies, both for taxane sensitive and taxane-insensitive tumors.