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ERBB oncogene proteins as targets for monoclonal antibodies

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Abstract

General properties of the family of tyrosine kinase ERBB receptors are considered in connection with their role in the generation of cascades of signal transduction in normal and tumor cells. Causes of acquisition of oncogene features by genes encoding these receptors and their role in tumorigenesis are analyzed. Anti-ERBB monoclonal antibodies approved for therapy are described in detail, and mechanisms of their antitumor activity and development of resistance to them are reviewed. The existing and the most promising strategies for creating and using monoclonal antibodies and their derivatives for therapy of cancer are discussed.

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Abbreviations

ADCC:

antibody-dependent cell cytotoxicity

BC:

breast cancer

EGF:

epidermal growth factor

EGFR:

epidermal growth factor receptor

ERBB:

avian erythroblastic leukemia viral oncogene homolog B (also EGFR/HER)

ERKs:

extracellular signal-regulated kinases

GPCRs:

G-protein coupled receptors

HER:

human epidermal growth factor receptor

IGF-IR:

insulin-like growth factor 1 receptor

JNKs:

c-Jun-N-terminal protein kinases

mAbs:

monoclonal antibodies

MAPKs:

mitogen-activated protein kinases

NLS:

nuclear localization signal

NRG:

neuregulin

NSCLC:

non-small cell lung cancer

PI3K:

phosphatidylinositol-3-kinase

PTEN:

phosphatase and tensin homolog

RTK:

receptor tyrosine kinase

SCCHN:

squamous cell carcinoma of head and neck

STATs:

proteins of signal transduction and activators of transcription

TGFα and TGFβ1:

transforming growth factors α and β1

VEGF and VEGFR:

vascular endothelial growth factor and its receptor

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991, Moscow, Russia

    O. L. Polanovski

  2. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia

    E. N. Lebedenko & S. M. Deyev

  3. Nizhny Novgorod State Medical Academy, pl. Minina i Pozharskogo 10/1, 603005, Nizhny Novgorod, Russia

    S. M. Deyev

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  1. O. L. Polanovski
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  2. E. N. Lebedenko
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  3. S. M. Deyev
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Correspondence to S. M. Deyev.

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Original Russian Text © O. L. Polanovski, E. N. Lebedenko, S. M. Deyev, 2012, published in Biokhimiya, 2012, Vol. 77, No. 3, pp. 289–311.

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Polanovski, O.L., Lebedenko, E.N. & Deyev, S.M. ERBB oncogene proteins as targets for monoclonal antibodies. Biochemistry Moscow 77, 227–245 (2012). https://doi.org/10.1134/S0006297912030029

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