- PROFESSOR Medicine, Liver Diseases
M.D., University of Barcelona
Hospital Germans Trias i Pujol
Josep M. Llovet is Director of the HCC Program and Professor of Medicine at the Mount Sinai School of Medicine, New York University (USA) and Professor of Research-ICREA in the BCLC Group, Liver Unit, IDIBAPS-Hospital Clínic of Barcelona (Spain), Professor Llovet obtained his degree in Medicine and Surgery from the University of Barcelona in 1986 and his PhD from the Autonomous University of Barcelona in 1995.
Professor Llovet was President of the International Liver Cancer Association (ILCA) 2011-2013 and Chairman of the European Clinical Practice Guidelines of management of liver cancer (EASL-EORTC). He has published more than 200 articles in peer-reviewed journals such as New England Journal of Medicine, Nature Genetics, Lancet, Cancer Cell, Journal Clinical Investigation, Journal of Clinical Oncology, Lancet Oncology, Gastroenterology and Hepatology (total citations 24.490, total impact factor 2176; h index 68), more than 40 chapters of books, and has delivered more than 400 lectures. He is Senior Editor of Clinical Cancer Research and Special Editor of Gastroenterology and Journal of Hepatology.
During the last 15 years, Dr. Llovet received the AACR-Landon International Award (2009) and the International Hans Popper award (2012), and is leading international projects with competitive funding from the European Comission (FP7- HEALTH, HEPTROMIC, 2010) and the US National Institute of Health (R01, 2008). Below, find described the scientific and managerial positions and the main scientific achievements obtained. He has contributed to advancing knowledge in the following areas.
1.Clinical classification of HCC: with the acronym BCLC (Barcelona-Clínic Liver Cancer) classification, first published in Llovet, Semin Liv Dis 1999, and then further modified in Llovet, Lancet 2003; Llovet, J Natl Can Inst, 2008 and Forner, Lancet 2012. This classification has been adopted by American (AASLD) and European (EASL-EORTC) guidelines of management of HCC.
2.Establishment of chemoembolization as standard of care in patients with 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. Adopted by American (AASLD) and European (EASL-EORTC) guidelines of management of HCC.
3. Establishment of sorafenib as standard of care in patients with advanced HCC (Llovet, New Engl J Med 2008). This breakthrough achievement establishes sorafenib as first line treatment for advanced HCC, and represents the first identification of survival advantages with systemic treatments. Identified by Nature Medicine as the most cited paper in oncology 2008-2010. Adopted by American (AASLD) and European (EASL-EORTC) guidelines of management of HCC.
4. Guidelines of management of HCC: Chair of EASL-EORTC Guidelines, 2012 (J Hepatol, 2012, Eur J Cancer 2012), and committee member of guidelines of EASL (2001). Leading author of AASLD guidelines for design of clinical trials in HCC (Llovet, J Natl Cancer Institute, 2008).
5.Establishment of a molecular diagnosis of HCC: Gene-set (3 genes) based diagnosis of HCC reported in Llovet, Gastroenterology 2006, and included in EASL-EORTC guidelines.
6. Proposal of a molecular classification of HCC and ICC: A final proposal of a molecular classification of HCC is based on the results reported in different publications (Wurmbach, Hepatology 2007; Hoshida, New Engl J Med, 2008, Chiang, Cancer Res, 2008; Hoshida, Cancer Res 2009, Villanueva, Gastroenterology 2011; Sia, Gastro 2013).
7. Identification of drivers of oncogenesis as targets for therapies. Several studies led to the identification of Akt/mTOR pathway [Villanueva Gastroenterology, 2008), Ras pathway (Newell, J Hepatol 2009), EGFR pathway (Keng, Nature Biotech 2009), IGF pathway ([Tovar, J Hepatol, 2011], Wnt Pathway (Lachenmeyer, CCR 2012), Notch pathway (Villanueva, Gastroenterology 2012), AEG (Yoo, J Clin Invest 2009) and miRNAs (Viswanathan, Nat Genetics 2009, Toffanin,Gastroenterology 2011] as drivers of hepatocarcinogenesis and potential targets for therapies.
Hepatocellular carcinoma, genomic researchAs Director of HCC Research of the Mount Sinai Liver Cancer Program, I'm currently involved in several research projects along with other investigators from the Division of Liver Diseases, the Recanati/Miller Transplantation Institute, the Center of Genomic Medicine, and the Division of Hematology and Medical Oncology (Department of Medicine). We have permanent international partners in the University of Barcelona (BCLC Group, Hospital Clinic) and the Instituto di Tumori in Milano. The main aim of the group is to assess the molecular pathogenesis of hepatocellular carcinoma, and the genes and pathways involved in the initiation and progression of the disease. In addition, we are investigating the molecular markers of early diagnosis and biomarkers of prognosis. The results will provide a molecular classification of HCC, and will allow us to identify targets for chemoprevention and treatment.
Hepatocellular carcinoma (HCC), clinical researchThe clinical research in liver cancer was carried out in the Liver Unit of the Hospital Clinic of Barcelona (1995-2003). We have published articles on the management of hepatocellular carcinoma (HCC), surgical treatment, living donor and cadaveric donor liver transplantation, percutaneous treatments, and systemic treatments in the setting of phase II-III-IV studies, meta-analysis and cost-effectiveness analysis. The most relevant aspects of the research are:
* Liver cancer classification and treatment strategy, with the acronym BCLC (Barcelona-Clinic Liver Cancer) Group, [Llovet et al Semin Liv Dis 1999, Bruix et al Hepatology 2002; Llovet et al Lancet 2003], which has been postulated as an optimal treatment approach to this neoplasm.
* Chemoembolization improves survival of patients with advanced HCC. Evidence-based statement through randomized controlled trials [Llovet et al, Lancet 2002] and meta-analysis [Llovet et al, Hepatology 2003] of survival advantages of chemoembolization in patients with unresectable HCC. This treatment is now considered the standard of care.
Llovet JM, Johnson PJ. Reply to X. Qi et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014 Feb;.
Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, Kang YK, Assenat E, Lim HY, Boige V, Mathurin P, Fartoux L, Lin DY, Bruix J, Poon RT, Sherman M, Blanc JF, Finn RS, Tak WY, Chao Y, Ezzeddine R, Liu D, Walters I, Park JW. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2013 Oct; 31(28).
Llovet JM, Bruix J. Testing molecular therapies in hepatocellular carcinoma: the need for randomized phase II trials. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009 Feb; 27(6).
Bruix J, Llovet JM. Major achievements in hepatocellular carcinoma. Lancet 2009 Feb; 373(9664).
Mudbhary R, Hoshida Y, Chernyavskaya Y, Jacob V, Villanueva A, Fiel MI, Chen X, Kojima K, Thung S, Bronson RT, Lachenmayer A, Revill K, Alsinet C, Sachidanandam R, Desai A, Senbanerjee S, Ukomadu C, Llovet JM, Sadler KC. UHRF1 Overexpression Drives DNA Hypomethylation and Hepatocellular Carcinoma. Cancer cell 2014 Feb; 25(2).
Villanueva A, Llovet JM. Liver cancer in 2013: Mutational landscape of HCC-the end of the beginning. Nature reviews. Clinical oncology 2014 Feb; 11(2).
Revill K, Wang T, Lachenmayer A, Kojima K, Harrington A, Li J, Hoshida Y, Llovet JM, Powers S. Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma. Gastroenterology 2013 Dec; 145(6).
Hernandez-Gea V, Alsinet C, Llovet JM. Oncolytic immunotherapeutic virus in HCC: can it compete with molecular therapies?. Journal of hepatology 2013 Oct; 59(4).
Nault JC, De Reyniès A, Villanueva A, Calderaro J, Rebouissou S, Couchy G, Decaens T, Franco D, Imbeaud S, Rousseau F, Azoulay D, Saric J, Blanc JF, Balabaud C, Bioulac-Sage P, Laurent A, Laurent-Puig P, Llovet JM, Zucman-Rossi J. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology 2013 Jul; 145(1).
Hoshida Y, Villanueva A, Sangiovanni A, Sole M, Hur C, Andersson KL, Chung RT, Gould J, Kojima K, Gupta S, Taylor B, Crenshaw A, Gabriel S, Minguez B, Iavarone M, Friedman SL, Colombo M, Llovet JM, Golub TR. Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis. Gastroenterology 2013 May; 144(5).
Sia D, Tovar V, Moeini A, Llovet JM. Intrahepatic cholangiocarcinoma: pathogenesis and rationale for molecular therapies. Oncogene 2013 Oct; 32(41).
Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology 2013 Mar; 144(3).
Sia D, Hoshida Y, Villanueva A, Roayaie S, Ferrer J, Tabak B, Peix J, Sole M, Tovar V, Alsinet C, Cornella H, Klotzle B, Fan JB, Cotsoglou C, Thung SN, Fuster J, Waxman S, Garcia-Valdecasas JC, Bruix J, Schwartz ME, Beroukhim R, Mazzaferro V, Llovet JM. Integrative molecular analysis of intrahepatic cholangiocarcinoma reveals 2 classes that have different outcomes. Gastroenterology 2013 Apr; 144(4).
Villanueva A, Llovet JM. Impact of intra-individual molecular heterogeneity in personalized treatment of hepatocellular carcinoma. Hepatology (Baltimore, Md.) 2012 Dec; 56(6).
Villanueva A, Hernandez-Gea V, Llovet JM. Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nature reviews. Gastroenterology & hepatology 2013 Jan; 10(1).
Toffanin S, Cornella H, Harrington A, Llovet JM. HCC Is promoted by bacterial translocation and TLR-4 signaling: a new paradigm for chemoprevention and management. Hepatology (Baltimore, Md.) 2012 Nov; 56(5).
Toffanin S, Cornella H, Harrington A, Llovet JM. Next-generation sequencing: path for driver discovery in hepatocellular carcinoma. Gastroenterology 2012 Nov; 143(5).
Villanueva A, Alsinet C, Yanger K, Hoshida Y, Zong Y, Toffanin S, Rodriguez-Carunchio L, Solé M, Thung S, Stanger BZ, Llovet JM. Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice. Gastroenterology 2012 Dec; 143(6).
Keng VW, Sia D, Sarver AL, Tschida BR, Fan D, Alsinet C, Solé M, Lee WL, Kuka TP, Moriarity BS, Villanueva A, Dupuy AJ, Riordan JD, Bell JB, Silverstein KA, Llovet JM, Largaespada DA. Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR. Hepatology (Baltimore, Md.) 2013 Jan; 57(1).
Lachenmayer A, Alsinet C, Savic R, Cabellos L, Toffanin S, Hoshida Y, Villanueva A, Minguez B, Newell P, Tsai HW, Barretina J, Thung S, Ward SC, Bruix J, Mazzaferro V, Schwartz M, Friedman SL, Llovet JM. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib. Clinical cancer research : an official journal of the American Association for Cancer Research 2012 Sep; 18(18).
Wang PR, Xu M, Toffanin S, Li Y, Llovet JM, Russell DW. Induction of hepatocellular carcinoma by in vivo gene targeting. Proceedings of the National Academy of Sciences of the United States of America 2012 Jul; 109(28).
Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, Galle PR, Santoro A, Beaugrand M, Sangiovanni A, Porta C, Gerken G, Marrero JA, Nadel A, Shan M, Moscovici M, Voliotis D, Llovet JM. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. Journal of hepatology 2012 Oct; 57(4).
Llovet JM, Peña CE, Lathia CD, Shan M, Meinhardt G, Bruix J. Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 2012 Apr; 18(8).
Villanueva A, Llovet JM. Second-line therapies in hepatocellular carcinoma: emergence of resistance to sorafenib. Clinical cancer research : an official journal of the American Association for Cancer Research 2012 Apr; 18(7).
Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012 Mar; 379(9822).
Lachenmayer A, Toffanin S, Cabellos L, Alsinet C, Hoshida Y, Villanueva A, Minguez B, Tsai HW, Ward SC, Thung S, Friedman SL, Llovet JM. Combination therapy for hepatocellular carcinoma: additive preclinical efficacy of the HDAC inhibitor panobinostat with sorafenib. Journal of hepatology 2012 Jun; 56(6).
Burrel M, Reig M, Forner A, Barrufet M, de Lope CR, Tremosini S, Ayuso C, Llovet JM, Real MI, Bruix J. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design. Journal of hepatology 2012 Jun; 56(6).
Villanueva A, Forns X, Llovet JM. Molecular epidemiology in HCV-related hepatocellular carcinoma: first steps. Journal of hepatology 2012 Jul; 57(1).
Forner A, Llovet JM, Bruix J. Chemoembolization for intermediate HCC: is there proof of survival benefit?. Journal of hepatology 2012 Apr; 56(4).
Villanueva A, Hoshida Y, Llovet JM. Hepatocellular carcinoma enters the sequencing era. Gastroenterology 2011 Nov; 141(5).
Llovet JM, Paradis V, Kudo M, Zucman-Rossi J. Tissue biomarkers as predictors of outcome and selection of transplant candidates with hepatocellular carcinoma. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2011 Oct; 17 Suppl 2.
Villanueva A, Llovet JM. Targeted therapies for hepatocellular carcinoma. Gastroenterology 2011 May; 140(5).
Raoul JL, Bruix J, Greten TF, Sherman M, Mazzaferro V, Hilgard P, Scherubl H, Scheulen ME, Germanidis G, Dominguez S, Ricci S, Nadel A, Moscovici M, Voliotis D, Llovet JM. Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses. Journal of hepatology 2012 May; 56(5).
Toffanin S, Hoshida Y, Lachenmayer A, Villanueva A, Cabellos L, Minguez B, Savic R, Ward SC, Thung S, Chiang DY, Alsinet C, Tovar V, Roayaie S, Schwartz M, Bruix J, Waxman S, Friedman SL, Golub T, Mazzaferro V, Llovet JM. MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a. Gastroenterology 2011 May; 140(5).
Villanueva A, Hoshida Y, Battiston C, Tovar V, Sia D, Alsinet C, Cornella H, Liberzon A, Kobayashi M, Kumada H, Thung SN, Bruix J, Newell P, April C, Fan JB, Roayaie S, Mazzaferro V, Schwartz ME, Llovet JM. Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma. Gastroenterology 2011 May; 140(5).
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Llovet during 2013 and/or 2014. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
- Bayer HealthCare Pharmaceuticals / Onyx Pharmaceuticals Partnership; Boehringer Ingelheim Corporation; Bristol-Myers Squibb; Daiichi-Sankyo Co., Ltd.; ImClone Systems (Eli Lilly and Company); Jennerex Biotherapeutics; Merck Serono; Merit Medical Systems Inc.; Novartis; Onyx Pharmaceuticals, Inc.
Scientific Advisory Board:
- Bayer HealthCare Pharmaceuticals / Onyx Pharmaceuticals Partnership
Other Activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership.
- Bayer HealthCare Pharmaceuticals / Onyx Pharmaceuticals Partnership; Bristol-Myers Squibb
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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