Document Detail

Optimizing treatment of metastatic colorectal cancer patients with anti-EGFR antibodies: overcoming the mechanisms of cancer cell resistance.
MedLine Citation:
PMID:  23281932     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: A number of anti-EGFR monoclonal antibodies (mAbs) have been recently developed for the treatment of refractory metastatic colorectal cancer (mCRC). These mAbs, blocking ligand/receptor interactions, exert their biological activity via multiple mechanisms, including inhibition of cell cycle progression, potentiation of cell apoptosis, inhibition of angiogenesis, tumor cell invasion and metastasis and, potentially, induction of immunological effector mechanisms.
AREAS COVERED: Cetuximab is an anti-EGFR mAb currently used in mCRC treatment. Despite the evidence of efficacy of cetuximab in the treatment of mCRC patients, the observation of low response rates was the proof of concept of resistance to anti-EGFR mAbs treatment. An increasing number of molecular alterations have been more recently hypothesized to be involved in resistance to anti-EGFR mAbs in CRC: mutations in BRAF, NRAS and PIK3CA, loss of expression of PTEN and, now, activation of HER2 signaling through HER2 gene amplification and/or increased heregulin stimulation.
EXPERT OPINION: This review focuses on the development of new strategies such as combination with other agents blocking alternative escape pathways, cancer cell prioritization hyperactivating EGFR pathway, combination with immune system, development of nanotech devices to increase efficacy of antibody-based therapy and overcome the mechanisms of cancer cell resistance.
Teresa Troiani; Silvia Zappavigna; Erika Martinelli; Santolo R Addeo; Paola Stiuso; Fortunato Ciardiello; Michele Caraglia
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2013-01-03
Journal Detail:
Title:  Expert opinion on biological therapy     Volume:  13     ISSN:  1744-7682     ISO Abbreviation:  Expert Opin Biol Ther     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-10     Completed Date:  2013-06-19     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101125414     Medline TA:  Expert Opin Biol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  241-55     Citation Subset:  IM    
Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale F. Magrassi e A. Lanzara, Seconda Università degli Studi di Napoli, Via S. Pansini 5, 80131 Napoli, Italia.
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MeSH Terms
Antibodies, Monoclonal / immunology,  therapeutic use*
Cell Transformation, Neoplastic
Colorectal Neoplasms / drug therapy*,  genetics,  pathology
Drug Resistance, Neoplasm / immunology*
Genes, ras
Neoplasm Metastasis
Receptor, Epidermal Growth Factor / immunology*
Reg. No./Substance:
0/Antibodies, Monoclonal; EC, Epidermal Growth Factor

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