The human EGFR (HER) family is essential for communication between many epithelial cancer cell types and the tumor microenvironment. Therapeutics targeting the HER family have demonstrated clinical success in the treatment of diverse epithelial cancers. Here we propose that the success of HER family–targeted monoclonal antibodies in cancer results from their ability to interfere with HER family consolidation of signals initiated by a multitude of other receptor systems. Ligand/receptor systems that initiate these signals include cytokine receptors, chemokine receptors, TLRs, GPCRs, and integrins. We further extrapolate that improvements in cancer therapeutics targeting the HER family are likely to incorporate mechanisms that block or reverse stromal support of malignant progression by isolating the HER family from autocrine and stromal influences.
H. Michael Shepard, Cathleen M. Brdlik, Hans Schreiber
Title and authors | Publication | Year |
---|---|---|
EGFR, HER2, and MET gene amplification and protein expression profiles in biliary tract cancer and their prognostic significance.
Kim Y, Jee S, Kim H, Paik SS, Choi D, Yoo SH, Shin SJ |
The oncologist | 2024 |
Extracellular vesicles derived from Akkermansia muciniphila promote placentation and mitigate preeclampsia in a mouse model
Chen Y, Ou Z, Pang M, Tao Z, Zheng X, Huang Z, Wen D, Li Q, Zhou R, Chen P, Situ B, Sheng C, Huang Y, Yue X, Zheng L, Huang L |
Journal of Extracellular Vesicles | 2023 |
Consensus for HER2 alterations testing in non-small-cell lung cancer
Ren S, Wang J, Ying J, Mitsudomi T, Lee DH, Wang Z, Chu Q, Mack PC, Cheng Y, Duan J, Fan Y, Han B, Hui Z, Liu A, Liu J, Lu Y, Ma Z, Shi M, Shu Y, Song Q, Song X, Song Y, Wang C, Wang X, Wang Z, Xu Y, Yao Y, Zhang L, Zhao M, Zhu B, Zhang J, Zhou C, Hirsch FR |
ESMO Open | 2022 |
Chinese expert consensus on the diagnosis and treatment of HER2‐altered non–small cell lung cancer
Zhang S, Wang W, Xu C, Zhang Y, Cai X, Wang Q, Song Z, Li Z, Yu J, Zhong W, Wang Z, Liu J, Liu A, Li W, Zhan P, Liu H, Lv T, Miao L, Min L, Lin G, Huang L, Yuan J, Jiang Z, Pu X, Rao C, Lv D, Yu Z, Li X, Tang C, Zhou C, Zhang J, Guo H, Chu Q, Meng R, Liu X, Wu J, Zhou J, Zhu Z, Pan W, Dong X, Pang F, Wang K, Yao C, Lin G, Li S, Yang Z, Luo J, Jia H, Nie X, Wang L, Zhu Y, Hu X, Xie Y, Lin X, Cai J, Xia Y, Feng H, Wang L, Du Y, Yao W, Shi X, Niu X, Yuan D, Yao Y, Kang J, Zhang J, Zhang C, Gao W, Huang J, Zhang Y, Sun P, Wang H, Ye M, Wang D, Wang Z, Wan B, Lv D, Yu G, Shi L, Xia Y, Gao F, Zhang X, Xu T, Zhou W, Wang H, Liu Z, Yang N, Wu L, Wang Q, Wang G, Hong Z, Wang J, Fang M, Fang Y, Zhang Y, Song Y, Ma S, Fang W, Lu Y |
Thoracic Cancer | 2022 |
Identifying the hub genes and immune infiltration related to pyroptosis in rheumatoid arthritis.
Xie W, Wu Z |
Medicine | 2021 |
Role of Heparin-Binding Epidermal Growth Factor-Like Growth Factor in Oxidative Stress-Associated Metabolic Diseases
S Kim, V Subramanian, A Abdel-Latif, S Lee |
Metabolic Syndrome and Related Disorders | 2020 |
Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism
Y Yan, J Xu, G Mao |
Medical science monitor : international medical journal of experimental and clinical research | 2020 |
Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis
S Kim, MJ Graham, RG Lee, L Yang, S Kim, V Subramanian, JD Layne, L Cai, RE Temel, D Shih, AJ Lusis, JA Berliner, S Lee |
Nutrition, Metabolism, and Cardiovascular Diseases | 2019 |
αvβ3-integrin regulates PD-L1 expression and is involved in cancer immune evasion
A Vannini, V Leoni, C Barboni, M Sanapo, A Zaghini, P Malatesta, G Campadelli-Fiume, T Gianni |
Proceedings of the National Academy of Sciences | 2019 |
Strategies for Delivery of siRNAs to Ovarian Cancer Cells
R Farra, M Maruna, F Perrone, M Grassi, F Benedetti, M Maddaloni, ME Boustani, S Parisi, F Rizzolio, G Forte, F Zanconati, M Cemazar, U Kamensek, B Dapas, G Grassi |
Pharmaceutics | 2019 |
The HER2 S310F Mutant Can Form an Active Heterodimer with the EGFR, Which Can Be Inhibited by Cetuximab but Not by Trastuzumab as well as Pertuzumab
JW Shin, S Kim, S Ha, B Choi, S Kim, SA Im, TY Yoon, J Chung |
Biomolecules | 2019 |
EGFR signaling pathway occupies an important position in cancer‐related downstream signaling pathways of Pyk2
T Shen, Q Guo |
Cell Biology International | 2019 |
Simultaneous targeting of EGFR, HER2, and HER4 by afatinib overcomes intrinsic and acquired cetuximab resistance in head and neck squamous cell carcinoma cell lines
ID Pauw, F Lardon, JV den Bossche, H Baysal, E Fransen, V Deschoolmeester, P Pauwels, M Peeters, JB Vermorken, A Wouters |
Molecular Oncology | 2018 |
Leveraging Genomics for Head and Neck Cancer Treatment
JD Kemmer, DE Johnson, JR Grandis |
Journal of dental research | 2018 |
Synergistic Targeting HER2 and EGFR with Bivalent Aptamer-siRNA Chimera Efficiently Inhibits HER2-Positive Tumor Growth
L Xue, NJ Maihle, X Yu, SC Tang, HY Liu |
Molecular Pharmaceutics | 2018 |
Targeting tumor cells with antibodies enhances anti-tumor immunity
Z Sun, YX Fu, H Peng |
Biophysics Reports | 2018 |
Amplification of Wild-type KRAS Imparts Resistance to Crizotinib in MET Exon 14 Mutant Non–Small Cell Lung Cancer
M Bahcall, MM Awad, LM Sholl, FH Wilson, M Xu, S Wang, S Palakurthi, J Choi, EV Ivanova, GC Leonardi, BC Ulrich, CP Paweletz, PT Kirschmeier, M Watanabe, H Baba, M Nishino, RJ Nagy, RB Lanman, M Capelletti, ES Chambers, AJ Redig, PA VanderLaan, DB Costa, Y Imamura, PA Jänne |
Clinical cancer research | 2018 |
The EGFR/miR-338-3p/EYA2 axis controls breast tumor growth and lung metastasis
Y Liang, X Xu, T Wang, Y Li, W You, J Fu, Y Liu, S Jin, Q Ji, W Zhao, Q Song, L Li, T Hong, J Huang, Z Lyu, Q Ye |
Cell Death and Disease | 2017 |
Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development
S Kim, L Yang, S Kim, RG Lee, MJ Graham, JA Berliner, AJ Lusis, L Cai, RE Temel, DL Rateri, S Lee, C Schulz |
PloS one | 2017 |
Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma
X Wang, H Niu, Q Fan, P Lu, C Ma, W Liu, Y Liu, W Li, S Hu, Y Ling, L Guo, J Ying, J Huang |
Oncotarget | 2016 |
The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M
S Zhao, H Li, Q Wang, C Su, G Wang, H Song, L Zhao, Z Luan, R Su |
BMC Cancer | 2015 |
Epidermal growth factor receptor protein overexpression and gene amplification are associated with aggressive biological behaviors of esophageal squamous cell carcinoma
G Lin, XJ Sun, QB Han, Z Wang, YP Xu, JL Gu, W Wu, G Zhang, JL Hu, WY Sun, WM Mao |
Oncology Letters | 2015 |
Bisphosphonates inactivate human EGFRs to exert antitumor actions
T Yuen, A Stachnik, J Iqbal, M Sgobba, Y Gupta, P Lu, G Colaianni, Y Ji, LL Zhu, SM Kim, J Li, P Liu, S Izadmehr, J Sangodkar, J Bailey, Y Latif, S Mujtaba, S Epstein, TF Davies, Z Bian, A Zallone, AK Aggarwal, S Haider, MI New, L Sun, G Narla, M Zaidi |
Proceedings of the National Academy of Sciences | 2014 |
Huntingtin-interacting protein 1 phosphorylation by receptor tyrosine kinases
HM Ames, AA Wang, A Coughran, K Evaul, S Huang, CW Graves, AA Soyombo, TS Ross |
Molecular and cellular biology | 2013 |
A novel isoform of the B cell tyrosine kinase BTK protects breast cancer cells from apoptosis: BTK in Breast Cancer
C Eifert, X Wang, L Kokabee, A Kourtidis, R Jain, MJ Gerdes, DS Conklin |
Genes, Chromosomes and Cancer | 2013 |
Gene amplification of EGFR, HER2, FGFR2 and MET in esophageal squamous cell carcinoma
H Kato, T Arao, K Matsumoto, Y Fujita, H Kimura, H Hayashi, K Nishiki, M Iwama, O Shiraishi, A Yasuda, M Shinkai, M Imano, H Imamoto, T Yasuda, K Okuno, H Shiozaki, K Nishio |
International journal of oncology | 2013 |
Adaptive Immune Responses and HER2/neu Positive Breast Cancer
ED Mortenson, YX Fu |
Current Pathobiology Reports | 2013 |
Therapeutic targeting of hyaluronan in the tumor stroma
A Kultti, X Li, P Jiang, CB Thompson, GI Frost, HM Shepard |
Cancers | 2012 |
CXCL12 and [N33A]CXCL12 in 5637 and HeLa Cells: Regulating HER1 Phosphorylation via Calmodulin/Calcineurin
A Rigo, M Gottardi, E Damiani, M Bonifacio, I Ferrarini, P Mauri, F Vinante |
PloS one | 2012 |
HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and activation of downstream signaling pathways
BK Choi, X Cai, B Yuan, Z Huang, X Fan, H Deng, N Zhang, Z An |
Protein & Cell | 2012 |
Epidermal growth factor receptor (EGFR) as a therapeutic target in rheumatoid arthritis
FL Yuan, X Li, WG Lu, JM Sun, DL Jiang, RS Xu |
Clinical Rheumatology | 2012 |
Dual Targeting of EGFR and HER3 with MEHD7945A Overcomes Acquired Resistance to EGFR Inhibitors and Radiation
S Huang, C Li, EA Armstrong, CR Peet, J Saker, LC Amler, MX Sliwkowski, PM Harari |
Cancer research | 2012 |
Lung cancer and Toll-like receptors
A Pinto, S Morello, R Sorrentino |
Cancer Immunology, Immunotherapy | 2011 |
Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells
M Dahl, P Bouchelouche, G Kramer-Marek, J Capala, J Nordling, K Bouchelouche |
Molecular Biology Reports | 2011 |
Human epidermal growth factor receptor bispecific ligand trap RB200: abrogation of collagen-induced arthritis in combination with tumour necrosis factor blockade
LL Gompels, NM Malik, L Madden, P Jin, M Feldmann, HM Shepard, EM Paleolog |
Arthritis Research & Therapy | 2011 |
Occludin is regulated by epidermal growth factor receptor activation in brain endothelial cells and brains of mice with acute liver failure
F Chen, T Hori, N Ohashi, AM Baine, CB Eckman, JH Nguyen |
Hepatology | 2011 |
Impact of oncogenic K-RAS on YB-1 phosphorylation induced by ionizing radiation
M Toulany, TA Schickfluss, W Eicheler, R Kehlbach, B Schittek, HP Rodemann |
Breast Cancer Research | 2011 |
Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion
A Belo, K Cheng, A Chahdi, J Shant, G Xie, S Khurana, JP Raufman |
AJP Gastrointestinal and Liver Physiology | 2011 |
Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer
C Berasain, MU Latasa, R Urtasun, S Goñi, M Elizalde, O Garcia-Irigoyen, M Azcona, J Prieto, MA Avila |
Cancers | 2011 |
SH3KBP1-binding protein 1 prevents epidermal growth factor receptor degradation by the interruption of c-Cbl-CIN85 complex: SH3KBP1-BINDING PROTEIN 1 AND EGFR DEGRADATION
L Feng, JT Wang, H Jin, K Qian, JG Geng |
Cell Biochemistry and Function | 2011 |
Anti-HER agents in gastric cancer: from bench to bedside
L Fornaro, M Lucchesi, C Caparello, E Vasile, S Caponi, L Ginocchi, G Masi, A Falcone |
Nature Reviews Gastroenterology & Hepatology | 2011 |
Lipocalin 2 is essential for chronic kidney disease progression in mice and humans
Amandine Viau, Khalil El Karoui, Denise Laouari, Martine Burtin, Clement Nguyen, Kiyoshi Mori, Evangeline Pillebout, Thorsten Berger, Tak W. Mak, Bertrand Knebelmann, Gerard Friedlander, Jonathan Barasch, Fabiola Terzi |
Journal of Clinical Investigation | 2010 |
Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways
NH Heintz, YM Janssen-Heininger, BT Mossman |
American journal of respiratory cell and molecular biology | 2010 |
Structure of the EGF receptor transactivation circuit integrates multiple signals with cell context
EJ Joslin, H Shankaran, LK Opresko, N Bollinger, DA Lauffenburger, HS Wiley |
Molecular BioSystems | 2010 |
Macrophages may promote cancer growth via a GM-CSF/HB-EGF paracrine loop that is enhanced by CXCL12
A Rigo, M Gottardi, A Zamò, P Mauri, M Bonifacio, M Krampera, E Damiani, G Pizzolo, F Vinante |
Molecular Cancer | 2010 |
Mechanistic insights into acquired drug resistance in epidermal growth factor receptor mutation‐targeted lung cancer therapy
Ji H |
Cancer Science | 2010 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy
E Martinelli, RD Palma, M Orditura, FD Vita, F Ciardiello |
Clinical & Experimental Immunology | 2009 |
Implications for KRAS status and EGFR-targeted therapies in metastatic CRC
N Normanno, S Tejpar, F Morgillo, AD Luca, EV Cutsem, F Ciardiello |
Nature Reviews Clinical Oncology | 2009 |
MANY CYTOKINES ARE VERY USEFUL THERAPEUTIC TARGETS IN DISEASE
Marc Feldmann |
Journal of Clinical Investigation | 2008 |