Reviews on Recent Clinical Trials

Alberto Zaniboni  
Oncologia Medica, Fondazione Poliambulanza


The Emerging Role of NRAS Mutations in Colorectal Cancer Patients Selected for Anti-EGFR Therapies

Author(s): Fausto Meriggi, William Vermi, Paola Bertocchi and Alberto Zaniboni

Affiliation: Medical Oncology Department, Fondazione Poliambulanza via Bissolati 57, 25124 Brescia, Italy.

Keywords: Colorectal cancer, epidermal growth factor receptor, mutations, KRAS, NRAS, anti-EGFR, monoclonal antibodies, cetuximab, panitumumab.


Colorectal cancer (CRC) is one of the most common cancers worldwide. Despite the improvement in overall survival (OS) due to new treatments and targeted therapies alone or in combination with chemotherapy up-to–date, little is known about cellular mechanisms, both of primary and acquired resistance of CRC to anti-Epidermal Growth Factor Receptor (EGFR) antibodies. EGFR is characterized by tyrosine kinase activity and occupies a key-role in the control of cellular transduction pathways. Its activation triggers both the RAS-RAF and PIK3CA pathways and is required to promote cell growth, differentiation, proliferation, and invasion. Cetuximab and panitumumab are both monoclonal antibodies (MoAbs) directed against the extracellular domain of EGFR, thus leading to inhibition of the downstream signaling pathways. Mutations in oncogene Kirsten-RAS (KRAS) are frequently associated with resistance to anti-EGFR therapy. However, a significant number of KRAS wild-type (WT) tumors fail to obtain disease control with anti-EGFR agents. Therefore, additional biomarkers of response/resistance to these drugs such as BRAF, NRAS, PIK3CA and PTEN have been investigated. This review will point attention on Neuroblastoma-RAS (NRAS) status in metastatic CRC (mCRC) patients (pts) selected for anti-EGFR therapy.

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Article Details

Page: [8 - 12]
Pages: 5
DOI: 10.2174/1568026614666140423121525