Abstract
The V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is frequently dysregulated in colorectal cancer (CRC). It is involved in the modulation of several downstream effectors, that include: Raf/Mek/Erk, PI3K/Akt, RalGDS/p38MAPK, and Rac/Rho, and thereby influences tumorigenesis, the invasive behaviors of tumor cell, and resistance to therapy. There is growing evidence exploring the use of drugs that target these pathways in the treatment of CRC. Cetuximab has been approved for CRC patients without a KRAS mutation, or for EGFR-expressing metastatic CRC, although some of the patients have a mutation of KRAS and NRAS. This review summarizes the recent knowledge about the therapeutic potential of targeting RAS with particular emphasis on recent preclinical and clinical studies in treatment of CRC.
Keywords:
KRAS; cetuximab; colorectal cancer; novel anticancer agent.
© 2017 Wiley Periodicals, Inc.
MeSH terms
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Antibodies, Monoclonal / therapeutic use
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Antineoplastic Agents, Immunological / therapeutic use*
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Cell Transformation, Neoplastic
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Cetuximab / therapeutic use*
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / pathology
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / genetics
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GTP Phosphohydrolases / antagonists & inhibitors
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GTP Phosphohydrolases / genetics
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Humans
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics
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Panitumumab
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Phenylurea Compounds / therapeutic use
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Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors*
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Proto-Oncogene Proteins p21(ras) / genetics*
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Proto-Oncogene Proteins p21(ras) / metabolism
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Pyridines / therapeutic use
Substances
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Antibodies, Monoclonal
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Antineoplastic Agents, Immunological
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KRAS protein, human
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Membrane Proteins
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Phenylurea Compounds
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Pyridines
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regorafenib
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Panitumumab
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EGFR protein, human
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ErbB Receptors
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GTP Phosphohydrolases
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NRAS protein, human
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Proto-Oncogene Proteins p21(ras)
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Cetuximab