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Resistance to the Anti-EGFR Therapy, Beyond KRAS, in Patients with Metastatic Colorectal Cancer

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Resistance to Immunotherapeutic Antibodies in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 2))

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Abstract

Several studies have shown that mutation profiles could influence the treatment decisions in patients with metastatic colorectal cancer (mCRC). It has been proven that patients with mutations in exon 2 of the KRAS ongogene gain no benefit from treatment with the monoclonal antibodies (moAbs) against Epidermal Growth Factor Receptor (EGFR), cetuximab and panitumumab. Currently, the determination of KRAS mutational status represents a paradigm for biomarkers development in the era of molecular targeted therapies. The current manuscript is an overview, which summarizes and critically reviews the clinical relevance of the proposed mechanism of resistance to beyond the KRAS exon 2 mutations, such as: KRAS outside codon 12 and 13, NRAS, BRAF V600E, PIK3CA exon 9 and 20 mutations, PTEN loss, EGFR ligands AREG, EREG mRNA expression and EGFR amplification. The aim is to identify molecular markers that might be used to select patients with the higher probability of response to anti-EGFR moAbs. Overall, the accumulating evidence of molecular biology of CRC has, substantially, changed the approach to mCRC and has given the clinicians more rational options for treating this illness.

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Abbreviations

AREG:

Affimetrix, Amphiregulin

EGFR:

Epidermal growth factor receptor

EREG:

Epiregulin

mCRC:

Metastatic colorectal cancer

moAbs:

Monoclonal antibodies

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Authors and Affiliations

  1. Department of Medical Oncology, University Hospital of Heraklion and Laboratory of Tumor Cell Biology, Medical School, University of Crete, Voutes and Stavrakia, 1352, 71110, Heraklion, Crete, Greece

    Zacharenia Saridaki & John Souglakos

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  1. Zacharenia Saridaki
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  2. John Souglakos
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Correspondence to John Souglakos .

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  1. Molecular Genetics, University of California, Los Angeles Dept. Microbiology, Immunology &, Los Angeles, California, USA

    Benjamin Bonavida

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Saridaki, Z., Souglakos, J. (2013). Resistance to the Anti-EGFR Therapy, Beyond KRAS, in Patients with Metastatic Colorectal Cancer. In: Bonavida, B. (eds) Resistance to Immunotherapeutic Antibodies in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7654-2_6

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