[1]
Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002; 31(4): 339-46.
[2]
Facciorusso A, Nacchiero MC, Rosania R, et al. Pathways and gene expression profiles in hepatocellular carcinoma. Minerva Gastroenterol Dietol 2012; 58(1): 35-48.
[3]
Santoro A, Rimassa L, Borbath I, et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 2013; 14(1): 55-63.
[4]
Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407: 249-57.
[5]
Maruotti N, Cantatore FP, Crivellato E, Vacca A, Ribatti D. Angiogenesis in rheumatoid arthritis. Histol Histopathol 2006; 21: 557-66.
[6]
Ribatti D, Vacca A, Nico B, Sansonno D, Dammacco F. Angiogenesis and anti-angiogenesis in hepatocellular carcinoma. Cancer Treat Rev 2006; 32: 437-44.
[7]
Uematsu S, Higashi T, Nouso K, et al. Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2005; 20: 583-8.
[8]
Montella L, Addeo R, Caraglia M, et al. Vascular endothelial growth factor monitoring in advanced hepatocellular carcinoma patients treated with radiofrequency ablation plus octreotide: a single center experience. Oncol Rep 2008; 20: 385-90.
[9]
Poon RT, Ng IO, Lau C, Yu WC, Fan ST, Wong J. Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma. Am J Surg 2001; 182: 298-304.
[10]
Hisai H, Kato J, Kobune M, et al. Increased expression of angiogenin in hepatocellular carcinoma in correlation with tumor vascularity. Clin Cancer Res 2003; 9: 4852-9.
[11]
Zhu AX. Systemic therapy of advanced hepatocellular carcinoma: how hopeful should we be? Oncologist 2006; 11: 790-800.
[12]
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-90.
[13]
Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004; 64: 7099-109.
[14]
Cheng AL, Kang YK, Chen Z, 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 2009; 10: 25-34.
[15]
Pinter M, Sieghart W, Graziadei I, et al. Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis. Oncologist 2009; 14: 70-6.
[16]
Yau T, Chan P, Ng KK, et al. Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response. Cancer 2009; 115: 428-36.
[17]
Abou-Alfa GK, Amadori D, Santoro A, et al. Is sorafenib (S) safe and effective in patients (pts) with hepatocellular carcinoma (HCC) and Child-Pugh B (CPB) cirrhosis? [abstract]. J Clin Oncol 2008; 26(15)(Suppl.): 4518.
[18]
Lacouture ME, Wu S, Robert C, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist 2008; 13: 1001-11.
[19]
Chu D, Lacouture ME, Fillos T, Wu S. Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis. Acta Oncol 2008; 47: 176-86.
[20]
Kudo M, Imanaka K, Chida N, et al. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer 2011; 47: 2117-27.
[21]
Je Y, Schutz FA, Choueiri TK. Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Lancet Oncol 2009; 10: 967-74.
[22]
Reig M, Torres F, Rodriguez-Lope C, et al. Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib. J Hepatol 2014; 61(2): 318-24.
[23]
Desar IM, Mulder SF, Stillebroer AB, et al. The reverse side of the victory: flare up of symptoms after discontinuation of sunitinib or sorafenib in renal cell cancer patients. A report of three cases. Acta Oncol 2009; 48: 927-31.
[24]
Schoenleber SJ, Kurtz DM, Talwalkar JA, et al. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and metaanalysis. Br J Cancer 2009; 100(9): 1385-92.
[25]
Abou-Alfa GK, Johnson P, Knox JJ, et al. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA 2010; 304(19): 2154-60.
[26]
Faris JE, Michaelson MD. Targeted therapies: sunitinib versus interferon-alpha in metastatic RCC. Nat Rev Clin Oncol 2010; 7(1): 7-8.
[27]
Zhu AX, Sahani DV, Duda DG, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 2009; 27(18): 3027-35.
[28]
Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 2006; 24(1): 25-35.
[30]
Jenab-Wolcott J, Giantonio BJ. Bevacizumab: current indications and future development for management of solid tumors. Expert Opin Biol Ther 2009; 9(4): 507-17.
[31]
Siegel AB, Cohen EI, Ocean A, et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol 2008; 26(18): 2992-8.
[32]
Malka D, Dromain C, Farace F. Bevacizumab in patients with advanced hepatocellular carcinoma (HCC): preliminary results of a phase II study with circulating endothelial cell (CEC) monitoring. J Clin Oncol 2007; 25(Suppl. 18): 4570.
[33]
Zhu AX, Blaszkowsky LS, Ryan DP, et al. Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006; 24(12): 1898-903.
[34]
Thomas MB, Morris JS, Chadha R, et al. Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J Clin Oncol 2009; 27(6): 843-50.
[35]
Bhide RS, Cai ZW, Zhang YZ, et al. Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J Med Chem 2006; 49: 2143-6.
[36]
Tille JC, Wood J, Mandriota SJ, et al. Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basic fibroblast growth factor-induced angiogenesis in vivo and in vitro. J Pharmacol Exp Ther 2001; 299: 1073-85.
[37]
Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 2008; 8: 592-603.
[38]
Park JW, Finn RS, Kim JS, et al. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2011; 17: 1973-83.
[39]
Finn RS, Kang YK, Mulcahy M, et al. Phase II, open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2012; 18(7): 2090-8.
[40]
Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology 2006; 43(2)(Suppl. 1): S45-53.
[41]
Kaposi-Novak P, Lee JS, Gomez-Quiroz L, et al. Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype. J Clin Invest 2006; 116(6): 1582-95.
[42]
You WK, McDonald DM. The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Rep 2008; 41: 833-9.
[43]
Zucali P, Santoro A, Rodriguez-Lope C, et al. Final results from ARQ 197-114: A phase Ib safety trial evaluating ARQ 197 in cirrhotic patients (pts) with hepatocellular carcinoma (HCC). J Clin Oncol 2010; 28 suppl: Abstract 4137.
[44]
Verslype C, Cohn AL, Kelley RK, et al. Activity of cabozantinib (XL184) in hepatocellular carcinoma: results from a randomized phase II discontinuation study. Proc Am Soc Clin Oncol 2012; 30 (suppl):: abstr 4007.
[45]
Villanueva A, Chiang DY, Newell P, et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008; 135(6): 1972-83.
[46]
Geissler EK, Schlitt HJ, Thomas G. mTOR, cancer and transplantation. Am J Transplant 2008; 8: 2212-8.
[47]
Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006; 124: 471-84.
[48]
Huynh H. Molecularly targeted therapy in hepatocellular carcinoma. Biochem Pharmacol 2010; 80: 550-60.
[49]
Chinnakotla S, Davis GL, Vasani S, et al. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl 2009; 15: 1834-42.
[50]
Albert DH, Tapang P, Magoc TJ, et al. Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther 2006; 5: 995-1006.
[51]
Philip PA, Mahoney MR, Allmer C, et al. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol 2005; 23(27): 6657-63.
[52]
Thomas MB, Chadha R, Glover K, et al. Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma. Cancer 2007; 110(5): 1059-67.
[53]
Cervello M, McCubrey JA, Cusimano A, et al. Targeted therapy for hepatocellular carcinoma: novel agents on the horizon. Oncotarget 2012; 3(3): 236-60.
[54]
Bekaii-Saab T, Markowitz J, Prescott N, et al. A multi-institutional phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas. Clin Cancer Res 2009; 15(18): 5895-901.
[55]
Ramanathan RK, Belani CP, Singh DA, et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol 2009; 64(4): 777-83.
[56]
Facciorusso A, Licinio R, Carr BI, Di Leo A, Barone M. MEK 1/2 inhibitors in the treatment of hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2015; 27: 1-11.
[57]
Facciorusso A, Muscatiello N, Di Leo A, Barone M. Combination therapy with sorafenib and radiofrequency ablation for hepatocellular carcinoma: a glimmer of light after the storm trial? Am J Gastroenterol 2015; 110(5): 770-1.