How melanoma tumours evade drug treatment
By ANIThursday, November 25, 2010
LONDON - A new research has discovered how some melanoma tumours evade drug treatment.
The findings by the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT pinpoint a critical gene called COT (also known as MAO3K8) involved in melanoma growth provide a framework for discovering ways to tackle cancer drug resistance.
“In melanoma as well as several other cancers, there is a critical need to understand resistance mechanisms, which will enable us to be smarter up front in designing drugs that can yield more lasting clinical responses,” said senior author Levi Garraway, of Dana-Farber and Harvard Medical School.
“Our work provides an unbiased method for approaching this problem not only for melanoma, but for any tumour type,” he added.
To explore the basis of this drug resistance, Garraway and his colleagues applied a systematic approach involving hundreds of different proteins called kinases.
From this work, the researchers identified several intriguing proteins, but the one that particularly stood out was COT.
While their initial findings were noteworthy, Garraway and his co-workers sought additional proof of the role of COT in melanoma drug resistance.
They analyzed human cancer cells, searching for ones that exhibit B-RAF mutations as well as elevated COT levels. The scientists successfully identified such “double positive” cells and further showed that the cells are indeed resistant to the effects of the RAF inhibitor.
“These were enticing results, but the gold standard for showing that something is truly relevant is to examine samples from melanoma patients,” said Garraway.
Garraway and his colleagues obtained three samples for analysis and in two out of three cases, COT gene levels became elevated following RAF inhibitor treatment or the development of drug resistance.
“Although we need to extend these results to larger numbers of samples, this is tantalizing clinical evidence that COT plays a role in at least some relapsing melanomas,” added Garraway.
The study is published in the journal Nature. (ANI)
