Research Progress on Anti-angiogenesis Drugs in Hepatocellular Carcinoma

¹ Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

² School of Pharmacy, Weifang Medical University, Weifang 261053, China

³ Aerospace Center Hospital, School of Aerospace Clinical Medicine, Peking University, Beijing 100049, China

⁴ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China

CP 2021, 3(2), 33–40;

© Invalid date by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

Download PDF

Cite

XML

Abstract

Primary liver cancer is the sixth most prevalent cancer worldwide and ranked in third for cancer-related mortality rate. Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers. High vascularization of HCC implies the significance of angiogenesis in the development and pathogenesis of HCC. Several angiogenic pathways have been identified as being dysregulated in HCC, highlighting potential therapeutic targets for the treatment of HCC. In 2007, sorafenib was approved as the standard first-line treatment for advanced HCC, catapulting the therapeutic approach of HCC into the avenue of targeted therapy. In recent years, the approval of several novel targeted drugs and the progress in combination of immunotherapy and targeted therapies provide more alternatives for the treatment of HCC. The progress of anti-angiogenesis therapies in HCC over the past few decades is reviewed and the future prospect of anti-angiogenesis therapy for HCC is also discussed.

Keywords

Hepatocellular carcinoma

Anti-angiogenesis

Targeted therapy

Combination treatment

Research progress

References

Sung H, Ferlay J, Siegel RL, et al., 2021, Global Cancer Statistics 2020: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 71:209–49. DOI: 10.3322/caac.21660.

Lan A, Hongmei Z, Rongshou Z, et al., 2019 Analysis of the Prevalence of liver Cancer in China in 2015. Chin J Cancer, 41:721–7.

Sia D, Villanueva A, Friedman SL, et al., 2017, Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis. Gastroenterology, 152:745–61. DOI: 10.1053/j.gastro.2016.11.048.

Hilmi M, Neuzillet C, Calderaro J, et al., 2019, Angiogenesis and Immune Checkpoint Inhibitors as Therapies for Hepatocellular Carcinoma: Current Knowledge and Future Research Directions. J Immunother Cancer, 7:333. DOI: 10.1186/s40425-019-0824-5.

Llovet JM, Zucman-Rossi J, Pikarsky E, et al., 2016, Hepatocellular Carcinoma. Nat Rev Dis Primers, 2:16018. DOI: 10.1038/nrdp.2016.18.

Zhu AX, Duda DG, Sahani DV, et al., 2011, HCC and Angiogenesis: Possible Targets and Future Directions. Nat Rev Clin Oncol, 8:292–301. DOI: 10.1038/nrclinonc.2011.30.

Dhanasekaran R, Venkatesh SK, Torbenson MS, et al., 2016, Clinical Implications of Basic Research in Hepatocellular Carcinoma. J Hepatol, 64:736–45. DOI: 10.1016/j.jhep.2016.02.036.

Morse MA, Sun W, Kim R, et al., 2019, The Role of Angiogenesis in Hepatocellular Carcinoma. Clin Cancer Res, 25:912–20.

Keating GM, 2017, Sorafenib: A Review in Hepatocellular Carcinoma. Target Oncol, 12:243–53.

Escudier B, Worden F, Kudo M, 2019, Sorafenib: Key Lessons from Over 10 Years of Experience. Expert Rev Anticancer Ther, 19:177–89. DOI: 10.1080/14737140.2019.1559058.

Llovet JM, Ricci S, Mazzaferro V, et al., 2008, Sorafenib in Advanced Hepatocellular Carcinoma. N Engl J Med, 359:378–90.

Cheng AL, Kang YK, Chen Z, et al., 2009, 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, 10:25–34. DOI: 10.1016/s1470-2045(08)70285-7.

Méndez-Blanco C, Fondevila F, García-Palomo A, et al., 2018, Sorafenib resistance in Hepatocarcinoma: Role of Hypoxia-Inducible Factors. Exp Mol Med, 50:1–9. DOI: 10.1038/s12276-018-0159-1.

Huang A, Yang X R, Chung WY, et al., 2020, Targeted Therapy for Hepatocellular Carcinoma. Signal Transduct Target Ther, 5:146.

Kudo M, Finn RS, Qin S, et al., 2018, Lenvatinib Versus Sorafenib in First-Line Treatment of Patients with Unresectable Hepatocellular Carcinoma: A Randomised Phase 3 Non-Inferiority Trial. Lancet. 391:1163–73. DOI: 10.1016/s0140-6736(18)30207-1.

Kobayashi M, Kudo M, Izumi N, et al., 2019, Cost-Effectiveness Analysis of Lenvatinib Treatment for Patients with Unresectable Hepatocellular Carcinoma (uHCC) Compared with Sorafenib in Japan. J Gastroenterol, 54:558–70. DOI: 10.1007/s00535-019-01554-0.

Lin YS, Yang H, Ding Y, et al., 2020, Donafenib in Progressive Locally Advanced or Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Results of a Randomized, Multicenter Phase II Trial. Thyroid, 31:607–15. DOI: 10.1089/thy.2020.0235.

Bi F, Qin S, Gu S, et al., 2020, Donafenib Versus Sorafenib as First-Line Therapy in Advanced Hepatocellular Carcinoma: An Open-Label, Randomized, Multicenter Phase II/III Trial. J Clin Oncol, 38:4506. DOI: 10.1200/jco.2020.38.15_suppl.4506.

Organized and Compiled by the Guiding Committee of the Chinese Society for Clinical Oncology, 2020, Guidelines for Diagnosis and Treatment of Primary Liver Cancer of CSCO. People’s Health Press, Beijing.

Bruix J, Qin S, Merle P, et al., 2017, Regorafenib for Patients with Hepatocellular Carcinoma Who Progressed on Sorafenib Treatment (RESORCE): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet, 389:56–66. DOI: 10.1016/s0140-6736(16)32453-9.

Llovet JM, Montal R, Sia D, et al., 2018, Molecular Therapies and Precision Medicine for Hepatocellular Carcinoma. Nat Rev Clin Oncol, 15:599–616. DOI: 10.1038/s41571-018-0073-4.

Personeni N, Rimassa L, Pressiani T, et al., 2019, Cabozantinib for the Treatment of Hepatocellular Carcinoma. Expert Rev Anticancer Ther, 19:847–55. DOI: 10.1080/14737140.2019.1674141.

Abou-Alfa GK, Meyer T, Cheng AL, et al., 2018, Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med, 379:54–63.

Zhang XH, Cao MQ, Li XX, et al., 2020, Apatinib as an Alternative Therapy for Advanced Hepatocellular Carcinoma. World J Hepatol, 12:766–74.

Li Q, Qin S, Gu S, et al., 2020, Apatinib as Second-Line Therapy in Chinese Patients with Advanced Hepatocellular Carcinoma: A Randomized, Placebo-Controlled, Double-Blind, Phase III Study. J Clin Oncol, 38:4507. DOI: 10.1200/jco.2020.38.15_suppl.4507.

Montal R, Andreu-Oller C, Bassaganyas L, et al., 2019, Molecular Portrait of High Alpha-Fetoprotein in Hepatocellular Carcinoma: Implications for Biomarker-Driven Clinical Trials. Br J Cancer, 121:340–3. DOI: 10.1038/s41416-019-0513-7.

Syed YY, 2020, Ramucirumab: A Review in Hepatocellular Carcinoma. Drugs, 80:315–22.

Zhu AX, Kang YK, Yen CJ, et al., 2019, Ramucirumab after Sorafenib in Patients with Advanced Hepatocellular Carcinoma and Increased a-Fetoprotein Concentrations (REACH-2): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet Oncol, 20:282–96. DOI: 10.3410/f.734883889.793574888.

Makker V, Taylor MH, Aghajanian C, et al., 2020, Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol, 38:2981–92.

Kawazoe A, Fukuoka S, Nakamura Y, et al., 2020, Lenvatinib Plus Pembrolizumab in Patients with Advanced Gastric Cancer in the First-Line or Second-Line Setting (EPOC1706): An Open-Label, Single-Arm, Phase 2 Trial. Lancet Oncol, 21:1057–65. DOI: 10.1016/s1470-2045(20)30271-0.

Motzer R, Alekseev B, Rha SY, et al., 2021, Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med, 384:1289–300.

Finn RS, Ikeda M, Zhu AX, et al., 2020, Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol, 38:2960–70.

Apolo AB, Nadal R, Girardi DM, et al., 2020, Phase I Study of Cabozantinib and Nivolumab Alone or with Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. J Clin Oncol, 38:3672–84.

Yau T, Zagonel V, Santoro A, et al., 2020, Nivolumab (NIVO)+Ipilimumab (IPI)+Cabozantinib (CABO) Combination Therapy in Patients (pts) with Advanced Hepatocellular Carcinoma (aHCC): Results from CheckMate 040. J Clin Oncol, 38:478. DOI: 10.1200/jco.2020.38.4_suppl.478.

Xu J, Shen J, Gu S, et al., 2021, Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (Rescue): A Nonrandomized, Open-Label, Phase II Trial. Clin Cancer Res, 27:1003–11. DOI: 10.1158/1078-0432.ccr-20-2571.

Bhoori S, Mazzaferro V, 2020, Combined Immunotherapy and VEGF-Antagonist in Hepatocellular Carcinoma: A Step Forward. Lancet Oncol, 21:740–1. DOI: 10.1016/s1470-2045(20)30211-4.

Girardi DM, Pacífico JP, Guedes DE, et al., 2020, Immunotherapy and Targeted Therapy for Hepatocellular Carcinoma: A Literature Review and Treatment Perspectives. Pharmaceuticals (Basel), 14:28. DOI: 10.3390/ph14010028.

Previous article in this issue

Next article in this issue

Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing