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Combined regimen brings new hope for patients with highly resistant metastatic colorectal cancer

TORINO, CANADA—A treatment might be on its way for patients with metastatic colorectal cancer who after failing initial chemotherapy also become refractory to agents targeting the epidermal growth factor receptor EGFR
While only 10 to 20% of patients with metastatic colorectal cancer have the genetic profile making them eligible for anti-EGFR therapy, unfortunately, even among these the best responders eventually become refractory. But in Science Translational Medicine, researchers have now reported that combining anti-EGFR agents to inhibitors of the MEK pathway might overturn this resistance.
And they suggest that a simple blood test could potentially reveal when patients are developing resistance.
Senior author Alberto Bardelli, from the University of Torino in Italy explained that next generation sequencing of DNA extracted from blood samples and tumors has empowered the investigators to look at one mutant allele in 10,000 wild-type alleles: “This detection in the blood will help clinicians to rationally devise the next level of therapy, ” he said.

Professor Bardelli’s team showed that anti-EGFR-resistance was due to the appearance of mutations that activate the MEK pathway. By treating resistant colon tumour cells with MEK-inhibitors, they managed to reverse resistance in pre-clinical experiments, and a human trial is on its way:
“The next step is to test — when we take patients and give them anti-EGFR therapy — [to see] if they respond, and if at relapse the addition of the new rationally devised drugs will interfere with the mechanism of resistance and give them benefit. ”

SOURCE: Misale S. et al., Blockade of EGFR and MEK Intercepts Heterogeneous Mechanisms of Acquired Resistance to Anti-EGFR Therapies in Colorectal Cancer, Sci Transl Med, 19 February 2014;6(224):224ra26, DOI: 10.1126/scitranslmed.3007947.
AUTHOR: Pr. Alberto Bardelli
Associate Professor of Molecular Genetics, Department of Oncology, University of Torino, 10060 Candiolo, Torino, Italy.

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