, We thank surgeons and pathologists at Henri Mondor hospital (APHP

J. Blanc, C. Balabaud, B. L. Bail, C. Laurent, J. Saric et al., Claire Castaing at Bordeaux Hospital; the "Réseau Français des biobanques des tumeurs hépatiques" Bruno Clément, Valérie Paradis, Thomas Decaens, Simone Mathoulin-Pelissier; the Cancer Biobank of CHU Bordeaux, no. BRIF: BB-0033-00036 and CHU Henri Mondor for contributing to the tissue collection. We thank Floriane Bard, Caroline Lecerf, Bérengère Ouine and Audrey Criqui for performing the RPPA experiments. We warmly thank Frédéric Soysouvanh for help in drug screening

J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers et al., Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012, Int J Cancer, vol.136, pp.359-86, 2015.

A. L. Cheng, Y. K. Kang, Z. Chen, C. J. Tsao, S. Qin et al., Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial, Lancet Oncol, vol.10, pp.25-34, 2009.

J. M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane et al., Sorafenib in advanced hepatocellular carcinoma, N Engl J Med, vol.359, pp.378-90, 2008.

J. Bruix, S. Qin, M. P. Granito, A. Huang, Y. H. Bodoky et al., Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial, Lancet, vol.389, pp.56-66, 2017.

N. Munshi, S. Jeay, Y. Li, C. R. Chen, D. S. France et al., ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity, Molecular cancer therapeutics, vol.9, pp.1544-53, 2010.

S. Giordano and A. Columbano, Met as a therapeutic target in HCC: facts and hopes, J Hepatol, vol.60, pp.442-52, 2014.

K. Schulze, S. Imbeaud, E. Letouze, L. B. Alexandrov, J. Calderaro et al.,

, Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets, Nat Genet, vol.47, pp.505-516, 2015.

K. Wang, H. Y. Lim, S. Shi, J. Lee, S. Deng et al., Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma, Hepatology, vol.58, pp.706-723, 2013.

A. Santoro, L. Rimassa, I. Borbath, D. B. Salvagni, S. Van-laethem et al.,

, Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study, Lancet Oncol, vol.14, pp.55-63, 2013.

C. Basilico, S. Pennacchietti, E. Vigna, C. Chiriaco, S. Arena et al.,

. Tivantinib, ARQ197) displays cytotoxic activity that is independent of its ability to bind MET, Clinical cancer research : an official journal of the American Association for Cancer Research, vol.19, pp.2381-92, 2013.

A. Calles, N. Kwiatkowski, B. K. Cammarata, D. Ercan, N. S. Gray et al., Tivantinib (ARQ 197) efficacy is independent of MET inhibition in non-small-cell lung cancer cell lines, Mol Oncol, vol.9, pp.260-269, 2015.

R. Katayama, A. Aoyama, T. Yamori, J. Qi, T. Oh-hara et al., Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition, Cancer Res, vol.73, pp.3087-96, 2013.

Q. Xiang, Z. Zhen, D. Y. Deng, J. Wang, Y. Chen et al., Tivantinib induces G2/M arrest and apoptosis by disrupting tubulin polymerization in hepatocellular carcinoma, J Exp Clin Cancer Res, vol.34, p.118, 2015.

S. Sagmeister, M. Eisenbauer, C. Pirker, T. Mohr, K. Holzmann et al., New cellular tools reveal complex epithelial-mesenchymal interactions in hepatocarcinogenesis, British journal of cancer, vol.99, pp.151-160, 2008.

J. C. Nault, A. De-reynies, A. Villanueva, J. Calderaro, S. Rebouissou et al., A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection, Gastroenterology, vol.145, pp.176-87, 2013.

S. Troncale, A. Barbet, L. Coulibaly, E. Henry, B. He et al., NormaCurve: a SuperCurve-based method that simultaneously quantifies and normalizes reverse phase protein array data, PloS one, vol.7, p.38686, 2012.

S. Boyault, D. S. Rickman, A. De-reynies, C. Balabaud, S. Rebouissou et al.,

, Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets, Hepatology, vol.45, pp.42-52, 2007.

J. C. Nault, M. Mallet, C. Pilati, J. Calderaro, P. Bioulac-sage et al., High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions, Nat Commun, vol.4, p.2218, 2013.

S. Y. Ha, J. Lee, S. Y. Kang, I. G. Do, S. Ahn et al., MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas, Mod Pathol, vol.26, pp.1632-1673, 2013.

A. Santoro, M. Simonelli, C. Rodriguez-lope, P. Zucali, L. H. Camacho et al.,

, A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis, British journal of cancer, vol.108, pp.21-25, 2013.

T. A. Yap, D. Olmos, A. T. Brunetto, N. Tunariu, J. Barriuso et al., Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies, Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol.29, pp.1271-1280, 2011.

B. Lutterbach, Q. Zeng, L. J. Davis, H. Hatch, G. Hang et al., Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival, Cancer Res, vol.67, pp.2081-2089, 2007.

Q. Xiang, W. Chen, M. Ren, J. Wang, H. Zhang et al., Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET, Clinical cancer research : an official journal of the American Association for Cancer Research, vol.20, pp.2959-70, 2014.

S. Z. Zhang, F. Y. Pan, J. F. Xu, J. Yuan, S. Y. Guo et al., Knockdown of c-Met by adenovirus-delivered small interfering RNA inhibits hepatocellular carcinoma growth in vitro and in vivo, Molecular cancer therapeutics, vol.4, pp.1577-84, 2005.

M. N. Stein, K. M. Hirshfield, H. Zhong, E. A. Singer, S. M. Ali et al., Response to crizotinib in a patient with MET-mutant papillary renal cell cancer after progression on tivantinib, Eur Urol, vol.67, pp.353-357, 2015.

S. Eathiraj, R. Palma, E. Volckova, M. Hirschi, D. S. France et al., Discovery of a novel mode of protein kinase inhibition characterized by the mechanism of inhibition of human mesenchymal-epithelial transition factor (c-Met) protein autophosphorylation by ARQ 197, The Journal of biological chemistry, vol.286, pp.20666-76, 2011.

R. Kanteti, I. Dhanasingh, I. Kawada, F. E. Lennon, Q. Arif et al., MET and PI3K/mTOR as a potential combinatorial therapeutic target in malignant pleural mesothelioma, PloS one, vol.9, p.105919, 2014.

S. Lu, H. P. Torok, E. Gallmeier, F. T. Kolligs, A. Rizzani et al., ARQ 197) affects the apoptotic and proliferative machinery downstream of c-MET: role of Mcl-1, Bcl-xl and Cyclin B1, Oncotarget, vol.6, pp.22167-78, 2015.

C. Reuther, V. Heinzle, M. Spampatti, G. Vlotides, E. De-toni et al., Cabozantinib and Tivantinib, but Not INC280, Induce Antiproliferative and Antimigratory Effects in Human Neuroendocrine Tumor Cells in vitro: Evidence for 'Off-Target' Effects Not Mediated by c-Met Inhibition, Neuroendocrinology, vol.103, pp.383-401, 2016.

Y. Zhou, C. Zhao, S. Gery, G. D. Braunstein, R. Okamoto et al., Off-target effects of c-MET inhibitors on thyroid cancer cells, Molecular cancer therapeutics, vol.13, pp.134-177, 2014.

Y. Horimoto, A. Arakawa, M. Tanabe, H. Sonoue, F. Igari et al., Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer, BMC Cancer, vol.14, p.550, 2014.

K. I. Kim, K. H. Lee, T. R. Kim, Y. S. Chun, T. H. Lee et al., Ki-67 as a predictor of response to neoadjuvant chemotherapy in breast cancer patients, J Breast Cancer, vol.17, pp.40-46, 2014.

A. Sueta, Y. Yamamoto, M. Hayashi, S. Yamamoto, T. Inao et al., Clinical significance of pretherapeutic Ki67 as a predictive parameter for response to neoadjuvant chemotherapy in breast cancer: is it equally useful across tumor subtypes?, Surgery, vol.155, pp.927-962, 2014.

Y. Chao, W. K. Chan, M. J. Birkhofer, O. Y. Hu, S. S. Wang et al., Phase II and pharmacokinetic study of paclitaxel therapy for unresectable hepatocellular carcinoma patients, British journal of cancer, vol.78, pp.34-43, 1998.

I. O. Ng, C. L. Liu, S. T. Fan, and M. Ng, Expression of P-glycoprotein in hepatocellular carcinoma. A determinant of chemotherapy response, Am J Clin Pathol, vol.113, pp.355-63, 2000.

E. L. Niero, B. Rocha-sales, C. Lauand, B. A. Cortez, M. M. De-souza et al., The multiple facets of drug resistance: one history, different approaches, J Exp Clin Cancer Res, vol.33, p.37, 2014.

M. M. Gottesman, T. Fojo, and S. E. Bates, Multidrug resistance in cancer: role of ATPdependent transporters, Nat Rev Cancer, vol.2, pp.48-58, 2002.

A. Aoyama, R. Katayama, T. Oh-hara, S. Sato, Y. Okuno et al., ARQ 197) exhibits antitumor activity by directly interacting with tubulin and overcomes ABC transporter-mediated drug resistance, Molecular cancer therapeutics, vol.13, pp.2978-90, 2014.

C. Porta, P. Giglione, A. Ferrari, F. Reversi, W. Liguigli et al., Tivantinib (ARQ197) in hepatocellular carcinoma, Expert review of anticancer therapy, vol.15, pp.615-637, 2015.

U. Mcdermott, S. V. Sharma, L. Dowell, P. Greninger, C. Montagut et al., Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling, Proc Natl Acad Sci U S A, vol.104, pp.19936-19977, 2007.

G. A. Smolen, R. Sordella, B. Muir, G. Mohapatra, A. Barmettler et al., Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752, Proc Natl Acad Sci, vol.103, pp.2316-2337, 2006.

M. P. Lolkema, H. H. Bohets, H. T. Arkenau, A. Lampo, E. Barale et al., The c-Met Tyrosine Kinase Inhibitor JNJ-38877605 Causes Renal Toxicity through Species-Specific Insoluble Metabolite Formation, Clinical cancer research : an official journal of the American Association for Cancer Research, vol.21, pp.2297-304, 2015.