Drug Resistant Cancers Have Alternative Drug Target
Monday, June 3, 2013 (Last Updated: 06/04/2013)
MONDAY, June 3 (HealthDay News) -- Cancers that develop resistance to anti-epidermal growth factor receptor (EGFR) treatments often have amplification of the MET gene, which can be targeted by drugs to overcome resistance, according to a study published online June 2 in Cancer Discovery.
Alberto Bardelli, Ph.D., from the Institute for Cancer Research and Treatment in Torino, Italy, and colleagues sequenced the DNA from three patients with colorectal cancer who initially responded to panitumumab- or cetuximab-based treatment (anti-EGFR) and relapsed without displaying mutations in the KRAS gene, which are associated with resistance in about half of cases.
The researchers found that the MET proto-oncogene was amplified, which could be detected in circulating tumor DNA before relapse. Xenografts of patient-derived colorectal cancer containing MET amplifications were resistant to anti-EGFR treatments, which could be overcome by treatment with MET kinase inhibitors.
"These results highlight the role of MET in mediating primary and secondary resistance to anti-EGFR therapies in colorectal cancer and encourage the use of MET inhibitors in patients displaying resistance as a result of MET amplification," Bardelli and colleagues conclude.
Several authors disclosed financial ties to pharmaceutical and diagnostic companies.
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