Cancers 2014, 6(3), 1540-1552; doi:10.3390/cancers6031540

Targeting MET Amplification as a New Oncogenic Driver

1email, 1,2,* email, 1,3email, 1,4email, 1email and 5email
Received: 21 May 2014; in revised form: 13 July 2014 / Accepted: 15 July 2014 / Published: 22 July 2014
(This article belongs to the Special Issue MET in Cancer)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.
Keywords: MET; gene amplification; non-small cell lung cancer; gastric cancer; fluorescence in situ hybridization (FISH); polymerase chain reaction (PCR); crizotinib
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MDPI and ACS Style

Kawakami, H.; Okamoto, I.; Okamoto, W.; Tanizaki, J.; Nakagawa, K.; Nishio, K. Targeting MET Amplification as a New Oncogenic Driver. Cancers 2014, 6, 1540-1552.

AMA Style

Kawakami H, Okamoto I, Okamoto W, Tanizaki J, Nakagawa K, Nishio K. Targeting MET Amplification as a New Oncogenic Driver. Cancers. 2014; 6(3):1540-1552.

Chicago/Turabian Style

Kawakami, Hisato; Okamoto, Isamu; Okamoto, Wataru; Tanizaki, Junko; Nakagawa, Kazuhiko; Nishio, Kazuto. 2014. "Targeting MET Amplification as a New Oncogenic Driver." Cancers 6, no. 3: 1540-1552.

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