Wednesday, November 25, 2015

CU Cancer Center study reports 'robust antitumor activity' of TAK-733 drug in mouse models of colorectal cancer

In continuation of my update on TAK-733

A University of Colorado Cancer Center study recently published online ahead of print in the journal Oncotarget reports "robust antitumor activity" of the drug TAK-733 in cells and mouse models of colorectal cancer. In all, 42 of 54 tested cell lines were sensitive to the drug, as were 15 of 20 tumors grown on mice from patient samples. Nine of these patient-derived tumors showed regression, meaning that tumor tumors shrank in response to the drug.

"This was a large preclinical study that showed good activity for the drug and gave preliminary evidence for a potential biomarker that could predict which tumors would respond best to the drug," says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of medical oncology at the University of Colorado School of Medicine.

Specifically, the drug intercedes in the MAPK signaling pathway, a cascade of cellular communication that controls cell growth and survival and is frequently altered in many cancers (especially including melanoma, non-small cell lung cancer, and colorectal cancer). The drug does this by silencing an essential link in this signaling chain, namely the molecule MEK. Without activity of the MEK kinase, MAPK signaling cannot occur and instead of surviving and proliferating, cancer cells dependent on this pathway die.

A handful of successful MEK kinase inhibitors exist, including trametinib and selumetinib.

"The preclinical results for TAK-733 were fairly impressive. We had high hopes that TAK-733 could be a next-generation MEK inhibitor that might support or replace the use of current drugs," Lieu says.

The study seemed a perfect precursor to a human clinical trial of TAK-733 in colorectal cancer.

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