. 2019 Sep; 17(1):33-48.
doi: 10.1038/s41571-019-0268-3.

HER2-targeted therapies - a role beyond breast cancer

Do-Youn Oh 1 Yung-Jue Bang 2 
  • PMID: 31548601
  •     65 citations


HER2 is an established therapeutic target in a large subset of women with breast cancer; a variety of agents including trastuzumab, pertuzumab, lapatinib, neratinib and trastuzumab emtansine (T-DM1) have been approved for the treatment of HER2-positive breast cancer. HER2 is also overexpressed in subsets of patients with other solid tumours. Notably, the addition of trastuzumab to first-line chemotherapy has improved the overall survival of patients with HER2-positive gastric cancer, and has become the standard-of-care treatment for this group of patients. However, trials involving pertuzumab, lapatinib and T-DM1 have failed to provide significant improvements in the outcomes of patients with HER2-positive gastric cancer. HER2-targeted therapies are also being tested in patients with other solid tumours harbouring HER2 overexpression, and/or amplifications or other mutations of the gene encoding HER2 (ERBB2), including biliary tract, colorectal, non-small-cell lung and bladder cancers. The experience with gastric cancer suggests that the successes observed in HER2-positive breast cancer might not be replicated in these other tumour types, owing to differences in the level of HER2 overexpression and other aspects of disease biology. In this Review, we describe the current role of HER2-targeted therapies beyond breast cancer and also highlight the potential of novel HER2-targeted agents that are currently in clinical development.

A multiomics comparison between endometrial cancer and serous ovarian cancer.
Hui Zhong, Huiyu Chen, +2 authors, Zhihui Wu.
PeerJ, 2020 Jan 17; 8. PMID: 31942259    Free PMC article.
Phenotypic changes of HER2-positive breast cancer during and after dual HER2 blockade.
Fara Brasó-Maristany, Gaia Griguolo, +25 authors, Aleix Prat.
Nat Commun, 2020 Jan 22; 11(1). PMID: 31959756    Free PMC article.
Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer: Updates and Challenges.
Eric Koncina, Serge Haan, Stefan Rauh, Elisabeth Letellier.
Cancers (Basel), 2020 Feb 06; 12(2). PMID: 32019056    Free PMC article.
Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models.
Regina Padmanabhan, Hadeel Shafeeq Kheraldine, +2 authors, Ala-Eddin Al Moustafa.
Cancers (Basel), 2020 Mar 14; 12(3). PMID: 32164163    Free PMC article.
Synthesis of a novel 89Zr-labeled HER2 affibody and its application study in tumor PET imaging.
Yuping Xu, Lizhen Wang, +6 authors, Min Yang.
EJNMMI Res, 2020 Jun 05; 10(1). PMID: 32495181    Free PMC article.
Comprehensive review of targeted therapy for colorectal cancer.
Yuan-Hong Xie, Ying-Xuan Chen, Jing-Yuan Fang.
Signal Transduct Target Ther, 2020 Apr 17; 5(1). PMID: 32296018    Free PMC article.
Fibroblast-tumor cell signaling limits HER2 kinase therapy response via activation of MTOR and antiapoptotic pathways.
Ioannis K Zervantonakis, Matthew D Poskus, +7 authors, Joan S Brugge.
Proc Natl Acad Sci U S A, 2020 Jul 01; 117(28). PMID: 32601199    Free PMC article.
Down-Regulation of USP8 Suppresses HER-3 Positive Gastric Cancer Cells Proliferation.
Jiangang Sun, Dandan Shen, +5 authors, Xiaoping Chen.
Onco Targets Ther, 2020 Aug 28; 13. PMID: 32848421    Free PMC article.
In vivo studies of a peptidomimetic that targets EGFR dimerization in NSCLC.
Leeza Shrestha, Sitanshu S Singh, +5 authors, Seetharama D Jois.
J Cancer, 2020 Sep 15; 11(20). PMID: 32922539    Free PMC article.
Managing therapeutic resistance in breast cancer: from the lncRNAs perspective.
Liyuan Peng, Jingwen Jiang, +3 authors, Na Xie.
Theranostics, 2020 Sep 16; 10(23). PMID: 32929354    Free PMC article.
Trial Watch: experimental TLR7/TLR8 agonists for oncological indications.
Giorgio Frega, Qi Wu, +4 authors, Oliver Kepp.
Oncoimmunology, 2020 Sep 17; 9(1). PMID: 32934889    Free PMC article.
Hsp90 inhibition and co-incubation with pertuzumab induce internalization and degradation of trastuzumab: Implications for use of T-DM1.
Marianne Skeie, Filip Nikolaysen, Ylenia Chitano, Espen Stang.
J Cell Mol Med, 2020 Jul 17; 24(17). PMID: 32672902    Free PMC article.
Screening and Identification of Key Biomarkers in Acquired Lapatinib-Resistant Breast Cancer.
Shengnan Bao, Yi Chen, +7 authors, Yongmei Yin.
Front Pharmacol, 2020 Oct 06; 11. PMID: 33013420    Free PMC article.
Serpin peptidase inhibitor clade A member 1-overexpression in gastric cancer promotes tumor progression in vitro and is associated with poor prognosis.
Longchang Jiang, Liangbiao George Hu.
Oncol Lett, 2020 Oct 06; 20(6). PMID: 33014156    Free PMC article.
Identification of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer by Using HER2-targeted 89Zr-Pertuzumab PET/CT.
Gary A Ulaner, Jorge A Carrasquillo, +9 authors, Jason S Lewis.
Radiology, 2020 Jun 10; 296(2). PMID: 32515679    Free PMC article.
Overview of current targeted therapy in gallbladder cancer.
Xiaoling Song, Yunping Hu, +3 authors, Yingbin Liu.
Signal Transduct Target Ther, 2020 Oct 09; 5(1). PMID: 33028805    Free PMC article.
High expression of squamous cell carcinoma antigen in poorly differentiated adenocarcinoma of the stomach: A case report.
Lin Wang, Lei Huang, +2 authors, Jie-Xin Zhang.
World J Clin Cases, 2020 Oct 22; 8(19). PMID: 33083420    Free PMC article.
Antibody-Targeted Imaging of Gastric Cancer.
Komal Mandleywala, Shayla Shmuel, Patricia M R Pereira, Jason S Lewis.
Molecules, 2020 Oct 15; 25(20). PMID: 33050602    Free PMC article.
8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy.
Ioannis A Voutsadakis.
J Clin Med, 2020 Sep 30; 9(10). PMID: 32987805    Free PMC article.
Pertuzumab and trastuzumab emtansine in patients with HER2-amplified metastatic colorectal cancer: the phase II HERACLES-B trial.
Andrea Sartore-Bianchi, Sara Lonardi, +22 authors, Salvatore Siena.
ESMO Open, 2020 Sep 30; 5(5). PMID: 32988996    Free PMC article.
Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer.
Shailendra K Gautam, Ranjana K Kanchan, +13 authors, Mohd Wasim Nasser.
Cancers (Basel), 2020 Oct 07; 12(10). PMID: 33019652    Free PMC article.
HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies.
Catalin Bogdan Satala, Ioan Jung, +5 authors, Simona Gurzu.
J Oncol, 2020 Nov 05; 2020. PMID: 33144857    Free PMC article.
Toward a Better Understanding of Bioassays for the Development of Biopharmaceuticals by Exploring the Structure-Antibody-Dependent Cellular Cytotoxicity Relationship in Human Primary Cells.
Sébastien Wieckowski, Cécile Avenal, +2 authors, Florian Cymer.
Front Immunol, 2020 Nov 17; 11. PMID: 33193318    Free PMC article.
A pan-cancer analysis of HER2 index revealed transcriptional pattern for precise selection of HER2-targeted therapy.
Ziteng Li, Siyuan Chen, +8 authors, Xiaodong Zhu.
EBioMedicine, 2020 Nov 09; 62. PMID: 33161227    Free PMC article.
Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future.
Long Li, Xiqun Zhu, +5 authors, Yuan Wu.
Front Immunol, 2020 Nov 24; 11. PMID: 33224149    Free PMC article.
Liquid biopsy and multi-analyte testing guided treatment of HER2 positive periampullary adenocarcinoma with durable complete response after trastuzumab based therapy.
Rajnish Nagarkar, Darshana Patil, +13 authors, Rajan Datar.
Oncotarget, 2020 Nov 24; 11(45). PMID: 33227091    Free PMC article.
Functionalized silk spheres selectively and effectively deliver a cytotoxic drug to targeted cancer cells in vivo.
Anna Florczak, Tomasz Deptuch, +5 authors, Hanna Dams-Kozlowska.
J Nanobiotechnology, 2020 Dec 03; 18(1). PMID: 33261651    Free PMC article.
Mechanisms and Future of Non-Small Cell Lung Cancer Metastasis.
Tianhao Zhu, Xunxia Bao, +6 authors, Sibo Zhu.
Front Oncol, 2020 Dec 03; 10. PMID: 33262947    Free PMC article.
Massively parallel sequencing analysis of 68 gastric-type cervical adenocarcinomas reveals mutations in cell cycle-related genes and potentially targetable mutations.
Pier Selenica, Barbara Alemar, +11 authors, Rajmohan Murali.
Mod Pathol, 2020 Dec 16; 34(6). PMID: 33318584    Free PMC article.
Interstitial pneumonitis related to trastuzumab deruxtecan, a human epidermal growth factor receptor 2-targeting Ab-drug conjugate, in monkeys.
Kazuyoshi Kumagai, Tetsuo Aida, +3 authors, Kazuhiko Mori.
Cancer Sci, 2020 Oct 15; 111(12). PMID: 33051938    Free PMC article.
An analysis of HER2 amplification in cervical adenocarcinoma: correlation with clinical outcomes and the International Endocervical Adenocarcinoma Criteria and Classification.
Haiyan Shi, Ying Shao, Weiguo Lu, Bingjian Lu.
J Pathol Clin Res, 2020 Oct 23; 7(1). PMID: 33089969    Free PMC article.
Quantification of Trastuzumab-HER2 Engagement In Vitro and In Vivo.
Alena Rudkouskaya, Jason T Smith, Xavier Intes, Margarida Barroso.
Molecules, 2020 Dec 23; 25(24). PMID: 33348564    Free PMC article.
Cancer vaccines: the importance of targeting oncogenic drivers and the utility of combinations with immune checkpoint inhibitors.
Erika J Crosby, H Kim Lyerly, Zachary C Hartman.
Oncotarget, 2021 Jan 19; 12(1). PMID: 33456706    Free PMC article.
Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials.
Nai-Jung Chiang, Li-Tzong Chen, +2 authors, Ming-Huang Chen.
Biomolecules, 2021 Jan 17; 11(1). PMID: 33451059    Free PMC article.
Breast cancer stem cells: A review of their characteristics and the agents that affect them.
Naing L Shan, Yoosub Shin, +2 authors, Nanjoo Suh.
Mol Carcinog, 2021 Jan 12; 60(2). PMID: 33428807    Free PMC article.
Sulforaphane: Expected to Become a Novel Antitumor Compound.
Geting Wu, Yuanliang Yan, +7 authors, Zhijie Xu.
Oncol Res, 2020 Mar 01; 28(4). PMID: 32111265    Free PMC article.
Genomic profiling of Chinese patients with urothelial carcinoma.
Bo Yang, Xiao Zhao, +7 authors, Shunchang Jiao.
BMC Cancer, 2021 Feb 17; 21(1). PMID: 33588785    Free PMC article.
Emerging trends in colorectal cancer: Dysregulated signaling pathways (Review).
Rehan Ahmad, Jaikee Kumar Singh, +3 authors, Sandeep Kumar Srivastava.
Int J Mol Med, 2021 Mar 04; 47(3). PMID: 33655327    Free PMC article.
AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.
Dowoon Gu, Seung Hyun Ahn, +8 authors, Sung Wook Chi.
Mol Ther Nucleic Acids, 2021 Mar 06; 23. PMID: 33664996    Free PMC article.
WEE1 inhibition reverses trastuzumab resistance in HER2-positive cancers.
Mei-Hua Jin, Ah-Rong Nam, +6 authors, Do-Youn Oh.
Gastric Cancer, 2021 Mar 17;. PMID: 33723720
Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer.
Jinghui Zhang, Jiajun Fan, +9 authors, Kai Yin.
Cell Death Dis, 2021 Mar 19; 12(4). PMID: 33731670    Free PMC article.
Cooperative treatment effectiveness of ATR and HSP90 inhibition in Ewing's sarcoma cells.
Christian Marx, Marc U Schaarschmidt, +14 authors, Zhao-Qi Wang.
Cell Biosci, 2021 Mar 22; 11(1). PMID: 33743824    Free PMC article.
Case Report: Trastuzumab Treatment in Adenosquamous Carcinoma of the Extrahepatic Biliary Tract With Her-2 Amplification.
Ye Hong, Xiaofen Li, Dan Cao.
Front Oncol, 2021 Mar 26; 11. PMID: 33763343    Free PMC article.
A Triptolide Loaded HER2-Targeted Nano-Drug Delivery System Significantly Suppressed the Proliferation of HER2-Positive and BRAF Mutant Colon Cancer.
Ayimukedisi Yalikong, Xu-Quan Li, +4 authors, Yun-Shi Zhong.
Int J Nanomedicine, 2021 Mar 30; 16. PMID: 33776436    Free PMC article.
Targeting loss of heterozygosity for cancer-specific immunotherapy.
Michael S Hwang, Brian J Mog, +12 authors, Kenneth W Kinzler.
Proc Natl Acad Sci U S A, 2021 Mar 19; 118(12). PMID: 33731480    Free PMC article.
A bivalent, bispecific Dab-Fc antibody molecule for dual targeting of HER2 and HER3.
Alexander Rau, Katharina Kocher, +8 authors, Oliver Seifert.
MAbs, 2021 Mar 24; 13(1). PMID: 33752566    Free PMC article.
Lipidated Peptidomimetic Ligand-Functionalized HER2 Targeted Liposome as Nano-Carrier Designed for Doxorubicin Delivery in Cancer Therapy.
Himgauri Naik, Jafrin Jobayer Sonju, +4 authors, Seetharama Jois.
Pharmaceuticals (Basel), 2021 Apr 04; 14(3). PMID: 33800723    Free PMC article.
Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage.
Tzu-Jung Yu, Yuan-Bin Cheng, +7 authors, Hsueh-Wei Chang.
Antioxidants (Basel), 2021 Apr 04; 10(3). PMID: 33807834    Free PMC article.
Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.
Katarzyna M Terlikowska, Bożena Dobrzycka, Sławomir J Terlikowski.
Int J Mol Sci, 2021 Apr 04; 22(7). PMID: 33800608    Free PMC article.
Prognostic Value of an Immunohistochemical Signature in Patients With Bladder Cancer Undergoing Radical Cystectomy.
Jie Wu, Jun-Miao Wen, +7 authors, Yi-Ping Zhu.
Front Oncol, 2021 Apr 13; 11. PMID: 33842349    Free PMC article.
Current updates on precision therapy for breast cancer associated brain metastasis: Emphasis on combination therapy.
Masoom Raza, Naveen Kumar, +5 authors, Seema Sehrawat.
Mol Cell Biochem, 2021 Apr 23;. PMID: 33886058
HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma.
Ziqi Jia, Jiahua Xing, +25 authors, Shanqing Li.
Transl Lung Cancer Res, 2021 Apr 24; 10(3). PMID: 33889517    Free PMC article.
Molecular Chaperone GRP94/GP96 in Cancers: Oncogenesis and Therapeutic Target.
Xiaofeng Duan, Stephen Iwanowycz, +3 authors, Bei Liu.
Front Oncol, 2021 Apr 27; 11. PMID: 33898309    Free PMC article.
Immuno-PET Detects Changes in Multi-RTK Tumor Cell Expression Levels in Response to Targeted Kinase Inhibition.
Patricia M R Pereira, Jalen Norfleet, Jason S Lewis, Freddy E Escorcia.
J Nucl Med, 2020 Jul 11; 62(3). PMID: 32646879    Free PMC article.
Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?
Angela Dalia Ricci, Alessandro Rizzo, +3 authors, Karim Rihawi.
Cancers (Basel), 2021 May 01; 13(7). PMID: 33916206    Free PMC article.
Cardiotoxicity of chemotherapy and targeted agents.
Todd William Mudd, Mansoor Khalid, Achuta Kumar Guddati.
Am J Cancer Res, 2021 May 06; 11(4). PMID: 33948350    Free PMC article.
The unpredictable carbon nanotube biocorona and a functionalization method to prevent protein biofouling.
Lorena García-Hevia, Mahsa Saramiforoshani, +6 authors, Mónica L Fanarraga.
J Nanobiotechnology, 2021 May 07; 19(1). PMID: 33952241    Free PMC article.
Genetic landscape of breast cancer and mutation tracking with circulating tumor DNA in Chinese women.
Yinghao Wang, Lizhi Lin, +19 authors, Ouchen Wang.
Aging (Albany NY), 2021 Apr 25; 13(8). PMID: 33893247    Free PMC article.
HER2-Targeted Immunotherapy and Combined Protocols Showed Promising Antiproliferative Effects in Feline Mammary Carcinoma Cell-Based Models.
Andreia Gameiro, Catarina Nascimento, Jorge Correia, Fernando Ferreira.
Cancers (Basel), 2021 May 01; 13(9). PMID: 33919468    Free PMC article.
Nanobodies for Medical Imaging: About Ready for Prime Time?
Léa Berland, Lauren Kim, +5 authors, Mohammad Rashidian.
Biomolecules, 2021 May 01; 11(5). PMID: 33925941    Free PMC article.
Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study.
Zhengbo Song, Dongqing Lv, +6 authors, Quan Lin.
Front Oncol, 2021 May 25; 11. PMID: 34026634    Free PMC article.
GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer.
Amanda N Lisby, John C Flickinger, +5 authors, Scott A Waldman.
Expert Rev Precis Med Drug Dev, 2021 May 25; 6(2). PMID: 34027103    Free PMC article.
Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches.
Punit Saraon, Shivanthy Pathmanathan, +3 authors, Igor Stagljar.
Oncogene, 2021 Jun 04;. PMID: 34079087
Ovarian cancer with high-level focal ERBB2 amplification responds to trastuzumab and pertuzumab.
Laure Thouvenin, Mélinda Charrier, +9 authors, Petros Tsantoulis.
Gynecol Oncol Rep, 2021 Jun 08; 37. PMID: 34095423    Free PMC article.