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The first clue of this came in a periodical published by ASCO in their September 1, 2011 issue of the ASCO Post about the obstacles that confront researchers in their efforts to develop effective combinations of targeted cancer agents.
Jane Perlmutter, PhD, pointed out that advances in genomics have provided sophisticated target therapies, but noted that cellular pathways contain redundancies that can be activated in response to inhibition of one or another pathway, thus promoting emergence of resistant cells and clinical relapse.
James Doroshow, MD, deputy director for clinical and translational research at the NCI, said, "the mechanism of actions for a growing number of targeted agents that are available for trials, are not completely understood. The lack of the right assays or imaging tools means inability to assess the target effect of many agents."
Michael T. Barrett, PhD, pointed out that "each patient's cancer could require it's own specific therapy." Kurt Bachman of GlaxoSmithKline, opined, "the challenge is to identify the tumor types most likely to respond, to find biomarkers that predict response, and to define the relationship of the predictors to biology of the inhibitors."
The complexities and redundancies of human tumor biology had finally dawned on these investigators. What they were describing was precisely the work that clinical oncologists involved with cell culture assays have been doing for the past two decades.
According to an article in the JNCI, it is becoming increasingly evident that cancers are dependent on a number of altered molecular pathways and can develop diverse mechanisms of resistance to therapy with single agents. Therefore, combination regimens may provide the best hope for effective therapies with durable effects.
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