Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012:6:221-31.
doi: 10.2147/BTT.S24217. Epub 2012 Jul 13.

Cetuximab and biomarkers in non-small-cell lung carcinoma

Affiliations

Cetuximab and biomarkers in non-small-cell lung carcinoma

Nitin Patil et al. Biologics. 2012.

Abstract

Cancer progression is a highly complex process that is driven by a constellation of deregulated signaling pathways and key molecular events. In non-small-cell lung cancer (NSCLC), as in several other cancer types, the epidermal growth factor receptor (EGFR) and its downstream signaling components represent a key axis that has been found not only to trigger cancer progression but also to support advanced disease leading to metastasis. Two major therapeutic approaches comprising monoclonal antibodies and small molecule tyrosine kinase inhibitors have so far been used to target this pathway, with a combination of positive, negative, and inconsequential results, as judged by patient survival indices. Since these drugs are expensive and not all patients derive benefits from taking them, it has become both pertinent and paramount to identify biomarkers that can predict not only beneficial response but also resistance. This review focuses on the chimeric monoclonal antibody, cetuximab, its application in the treatment of NSCLC, and the biomarkers that may guide its use in the clinical setting. A special emphasis is placed on the EGFR, including its structural and mechanistic attributes.

Keywords: NSCLC; biomarker; cancer progression; cetuximab.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The EGFR signaling cascade. Notes: Schematic representation of the EGFR signaling axis including its most important downstream targets. Molecular categories are as shown in the color scheme. A direct arrow represents direct interaction, dotted arrows represent translocation into different subcellular compartments, and blunted line represents inhibitory effects. The grey broken line represents the interface between cytoplasm and nucleus. Abbreviation: EGFR, epidermal growth factor receptor.
Figure 2
Figure 2
The mechanism of cetuximab action. Notes: Schematic representation of how cetuximab mediates its antitumor activity. The antibody binding to epidermal growth factor receptor prevents receptor dimerization, leading to inhibition of receptor function as shown. Cetuximab binding also fosters receptor internalization and promotes antibody-dependent cell cytotoxicity. The resulting outcomes include disruption of apoptosis,,,, angiogenesis,,,, proliferation,,, invasion,,, and metastasis.,,, Abbreviation: EGFR, epidermal growth factor receptor.

Similar articles

Cited by

References

    1. Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10. Lyon, France: International Agency for Research on Cancer; 2010. http://globocan.iarc.fr. Accessed May 24, 2011.
    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–2917. - PubMed
    1. Laskin JJ, Sandler AB, Johnson DH. Non-Small Cell Lung Cancer. Philadelphia, PA: Saunders; 2005.
    1. Alberg AJ, Brock MV, Samet JM. Epidemiology of lung cancer: looking to the future. J Clin Oncol. 2005;23(14):3175–3185. - PubMed
    1. Vineis P, Airoldi L, Veglia F, et al. Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study. BMJ. 2005;330(7486):277. - PMC - PubMed