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Journal ArticleDOI

ERBB receptors and cancer: the complexity of targeted inhibitors.

TLDR
This work discusses the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response, and many ERBB inhibitors used in the clinic.
Abstract
ERBB receptor tyrosine kinases have important roles in human cancer. In particular, the expression or activation of epidermal growth factor receptor and ERBB2 are altered in many epithelial tumours, and clinical studies indicate that they have important roles in tumour aetiology and progression. Accordingly, these receptors have been intensely studied to understand their importance in cancer biology and as therapeutic targets, and many ERBB inhibitors are now used in the clinic. We will discuss the significance of these receptors as clinical targets, in particular the molecular mechanisms underlying response.

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Journal ArticleDOI

Cancer Genome Landscapes

TL;DR: This work has revealed the genomic landscapes of common forms of human cancer, which consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of "hills" (Genes altered infrequently).
Journal ArticleDOI

Matrix Metalloproteinases: Regulators of the Tumor Microenvironment

TL;DR: In addition to their role in extracellular matrix turnover and cancer cell migration, MMPs regulate signaling pathways that control cell growth, inflammation, or angiogenesis and may even work in a nonproteolytic manner.
Journal ArticleDOI

Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer

TL;DR: Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors, and KRAS status should be considered in selecting patients withmCRC as candidates for panitumuab mon Therapy.
References
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Journal Article

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition Augments a Murine Model of Pulmonary Fibrosis

TL;DR: The results suggest that the inhibition of EGFR phosphorylation augments bleomycin-induced pulmonary fibrosis by reducing regenerative epithelial proliferation, and EGFR-TKIs should be used with caution in cancer patients with lung fibrosis.
Journal Article

Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2-overexpressing breast cancer cells.

TL;DR: Observations support the concept that simultaneously co-targeting tyrosine kinase receptors may be therapeutically useful, and provide a specific rationale for combining IGF-1R and HER2/erbB2 targeting strategies in anti-neoplastic approaches.
Journal ArticleDOI

Blockade of epidermal growth factor- or heregulin-dependent ErbB2 activation with the anti-ErbB2 monoclonal antibody 2C4 has divergent downstream signaling and growth effects.

TL;DR: ErbBB2 is identified as a critical component of EGF signaling to the Gab1/Gab2-PI3K-Akt pathway and anchorage-independent growth, but EGF stimulation of MAPK and monolayer growth can occur efficiently without the contribution of ErbB2.
Journal ArticleDOI

Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins.

TL;DR: The results showed that Grb2 recruitment to site 1144 is absolutely required for transforming signal from this autophosphorylation site, whereas association of Shc-mediated transformation is dependent on conservation of the NPXY motif spanning Tyr1227.
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Overcoming Endocrine Therapy Resistance by Signal Transduction Inhibition

TL;DR: Preliminary data from a small "proof of concept" phase II study of letrozole and trastuzumab demonstrated durable responses despite tamoxifen resistance, however, efficacy was variable, despite the selection of patients on the basis of ER and ErbB-2 coexpression.
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