Research lines

  • Translational research in liver cancer

    Our scientific contributions to advancing knowledge in liver cancer during the last 15 years are summarized as follows: we defined a molecular classification of HCC, dissected the role of several signaling pathways (mTOR, Notch, Wnt and IGF signaling) in the pathogenesis of HCC, discovered new drivers (IGF2 and FGFR2 fusions) for HCC and cholangiocarcinoma, and provided transcriptomic and methylomic-based prognostic signatures in HCC.

  • Establishment of a molecular diagnosis and classification of HCC

    Gene-set (three genes) based diagnosis of HCC reported in Llovet, Gastroenterology 2006, and included in EASL-EORTC guidelines. In addition, we proposed a molecular classification of HCC based on the results reported in different publications.

  • Identification of drivers of oncogenesis as targets for therapies in HCC

    Several studies led to the identification of Akt/mTOR pathway [Villanueva Gastroenterology, 2008),  EGFR pathway (Keng, Nature Biotech 2009), IGF pathway ([Martinez-Quetglas, Gastroenterology 2016], Wnt Pathway (Lachenmeyer, CCR 2012), Notch pathway (Villanueva, Gastroenterology 2012), AEG (Yoo, J Clin Invest 2009), UHRF1 (Mudbhary R,Cancer Cell 2014)  and miRNAs (Viswanathan, Nat Genetics 2009, Toffanin, Gastroenterology 2011]. Also identification of mutational signatures associated with genotoxic (alcohol and tobacoo) in HCC (Schulze K, Nature Genetics 2015).

  • Identification of drivers of oncogenesis as targets for therapies in iCCA

    We identified IDH mutations as gatekeeper drivers in progenitor cells (Saha, Nature, 2014) and FGFR2 fusion proteins as oncodrivers and novel targets for therapies in ICC (Sia, Nature Communications 2015).

  • Establishment of chemoembolization, sorafenib, regorafenib and ramucirumab as standard of care in HCC patients. Intermediate HCC

    Evidence-based establishment through randomized controlled trials [Llovet, Lancet 2002] and meta-analysis [Llovet, Hepatology 2003] of chemoembolization as standard of care in patients with intermediate HCC. Advanced HCC: International RCT showing survival benefits for sorafenib vs placebo, presented at plenary session in ASCO. (Llovet, New Engl J Med 2008), and recently regorafenib and ramucirumab in second-line treatment. 

    This breakthrough achievement establishes sorafenib as first line treatment for advanced HCC, and represents the first identification of survival advantages with systemic treatments. Adopted by American (AASLD) and European (EASL-EORTC) guidelines of management of HCC.