Lenvatinib for hepatocellular carcinoma: From preclinical mechanisms to anti-cancer therapy

被引：167

作者：

Zhao, Yan ^{[1
,3
]}

Zhang, Ya-Ni ^{[1
]}

Wang, Kai-Ting ^{[1
]}

Chen, Lei ^{[2
,4
]}

机构：

[1] Fudan Univ, Sch Life Sci, Shanghai 200438, Peoples R China

[2] Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai, Peoples R China

[3] 2005 Songhu Rd, Shanghai 200438, Peoples R China

[4] 225 Changhai Rd, Shanghai 200438, Peoples R China

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2020年 / 1874卷 / 01期

基金：

中国国家自然科学基金; 上海市自然科学基金;

关键词：

Lenvatinib; HCC; Molecular mechanisms; Clinical efficacy; Precision medicine; ENDOTHELIAL GROWTH-FACTOR; SUPPRESSES TUMOR-GROWTH; FACTOR-RECEPTOR; ANTITUMOR ACTIVITIES; CLINICAL-OUTCOMES; T-CELLS; SORAFENIB; CANCER; BEVACIZUMAB; INHIBITOR;

D O I：

10.1016/j.bbcan.2020.188391

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), is an emerging first-line therapy for hepatocellular carcinoma (HCC). Its application has changed the status of sorafenib as the only first-line TKI treatment for HCC for more than a decade. Evidence has shown that lenvatinib possesses antitumor proliferation and immunomodulatory activity in preclinical studies. In comparison, lenvatinib was non-inferior to sorafenib in overall survival (OS), and even shows superiority with regard to all the secondary efficacy endpoints. Immune-checkpoint inhibitors(ICIs)are now being incorporated into HCC treatment. Positive outcomes have been achieved in the combination of lenvatinib plus ICIs, bringing broader prospects for HCC. This review presents an overview on the therapeutic mechanisms and clinical efficacy of lenvatinib in HCC, and we discuss the future perspectives of lenvatinib in HCC management with focus on biomarker-guided precision medicine.

引用

页数：9

共 96 条

[1] Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma [J].

Abou-Alfa, G. K. ;

Meyer, T. ;

Cheng, A. -L. ;

El-Khoueiry, A. B. ;

Rimassa, L. ;

Ryoo, B. -Y. ;

Cicin, I. ;

Merle, P. ;

Chen, Y. H. ;

Park, J. -W. ;

Blanc, J. -F. ;

Bolondi, L. ;

Klumpen, H. -J. ;

Chan, S. L. ;

Zagonel, V. ;

Pressiani, T. ;

Ryu, M. -H. ;

Venook, A. P. ;

Hessel, C. ;

Borgman-Hagey, A. E. ;

Schwab, G. ;

Kelley, R. K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (01) :54-63

[2] Anti-angiogenic agents for the treatment of solid tumors: Potential pathways, therapy and current strategies - A review [J].

Al-Abd, Ahmed M. ;

Alamoudi, Abdulmohsin J. ;

Abdel-Naim, Ashraf B. ;

Neamatallah, Thikryat A. ;

Ashour, Osama M. .

JOURNAL OF ADVANCED RESEARCH, 2017, 8 (06) :591-605

[3] RET tyrosine kinase signaling in development and cancer [J].

Arighi, E ;

Borrello, MG ;

Sariola, H .

CYTOKINE & GROWTH FACTOR REVIEWS, 2005, 16 (4-5) :441-467

[4] Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial [J].

Bruix, Jordi ;

Qin, Shukui ;

Merle, Philippe ;

Granito, Alessandro ;

Huang, Yi-Hsiang ;

Bodoky, Gyrogy ;

Pracht, Marc ;

Yokosuka, Osamu ;

Rosmorduc, Olivier ;

Breder, Valeriy ;

Gerolami, Rene ;

Masi, Gianluca ;

Ross, Paul J. ;

Song, Tianqiang ;

Bronowicki, Jean-Pierre ;

Ollivier-Hourmand, Isabelle ;

Kudo, Masatoshi ;

Cheng, Ann-Lii ;

Llovet, Josep M. ;

Finn, Richard S. ;

LeBerre, Marie-Aude ;

Baumhauer, Annette ;

Meinhardt, Gerold ;

Han, Guohong .

LANCET, 2017, 389 (10064) :56-66

[5] Linifanib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: Results of a Randomized Phase III Trial [J].

Cainap, Calin ;

Qin, Shukui ;

Huang, Wen-Tsung ;

Chung, Ik Joo ;

Pan, Hongming ;

Cheng, Ying ;

Kudo, Masatoshi ;

Kang, Yoon-Koo ;

Chen, Pei-Jer ;

Toh, Han-Chong ;

Gorbunova, Vera ;

Eskens, Ferry A. L. M. ;

Qian, Jiang ;

McKee, Mark D. ;

Ricker, Justin L. ;

Carlson, Dawn M. ;

El-Nowiem, Saied .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (02) :172-U77

[6] Sunitinib Versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III Trial [J].

Cheng, Ann-Lii ;

Kang, Yoon-Koo ;

Lin, Deng-Yn ;

Park, Joong-Won ;

Kudo, Masatoshi ;

Qin, Shukui ;

Chung, Hyun-Cheol ;

Song, Xiangqun ;

Xu, Jianming ;

Poggi, Guido ;

Omata, Masao ;

Lowenthal, Susan Pitman ;

Lanzalone, Silvana ;

Yang, Liqiang ;

Lechuga, Maria Jose ;

Raymond, Eric .

JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (32) :4067-+

[7] Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma [J].

Chuma, Makoto ;

Uojima, Haruki ;

Numata, Kazushi ;

Hidaka, Hisashi ;

Toyoda, Hidenori ;

Hiraoka, Atsushi ;

Tada, Toshifumi ;

Hirose, Shunji ;

Atsukawa, Masanori ;

Itokawa, Norio ;

Arai, Taeang ;

Kako, Makoto ;

Nakazawa, Takahide ;

Wada, Naohisa ;

Iwasaki, Shuitirou ;

Miura, Yuki ;

Hishiki, Satoshi ;

Nishigori, Shuhei ;

Morimoto, Manabu ;

Hattori, Nobuhiro ;

Ogushi, Katsuaki ;

Nozaki, Akito ;

Fukuda, Hiroyuki ;

Kagawa, Tatehiro ;

Michitaka, Kojiro ;

Kumada, Takashi ;

Maeda, Shin .

CANCERS, 2020, 12 (02)

[8] Genetic Biomarkers For Hepatocellular Carcinoma In The Era Of Precision Medicine [J].

Duan, Jingxian ;

Wu, Yuling ;

Liu, Jikui ;

Zhang, Jiajia ;

Fu, Zhichao ;

Feng, Tieshan ;

Liu, Ming ;

Han, Jie ;

Li, Zhicheng ;

Chen, Shifu .

JOURNAL OF HEPATOCELLULAR CARCINOMA, 2019, 6 :151-166

[9] Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial [J].

El-Khoueiry, Anthony B. ;

Sangro, Bruno ;

Yau, Thomas ;

Crocenzi, Todd S. ;

Kudo, Masatoshi ;

Hsu, Chiun ;

Kim, Tae-You ;

Choo, Su-Pin ;

Trojan, Jorg ;

Welling, Theodore H., III ;

Meyer, Tim ;

Kang, Yoon-Koo ;

Yeo, Winnie ;

Chopra, Akhil ;

Anderson, Jeffrey ;

dela Cruz, Christine ;

Lang, Lixin ;

Neely, Jaclyn ;

Tang, Hao ;

Dastani, Homa B. ;

Melero, Ignacio .

LANCET, 2017, 389 (10088) :2492-2502

[10] Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis [J].

El-Serag, Hashem B. ;

Rudolph, Lenhard .

GASTROENTEROLOGY, 2007, 132 (07) :2557-2576

← 1 2 3 4 5 6 7 8 9 10 →