DOI: 10.1097/01.COT.0000410203.68928.81

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Issn Print: 0276-2234

Publication Date: 2011/12/10


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‘FRESH SCIENCE for Clinicians’: Overcoming Molecular Resistance: New Insights, New Frustrations

Rabiya S. Tuma

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Excerpt

SAN FRANCISCO—As of yet, few molecularly targeted therapies provide more than a short reprieve for patients with advanced cancer, since resistance develops quickly even in patients with a strong initial response. And although numerous investigators are working in tissue culture cells and model systems to uncover the mechanisms of resistance, Jeffrey A. Engelman, MD, PhD, and colleagues have taken their work right to patients, work described here at the AACR International Conference on Frontiers in Basic Cancer Research meeting.
The results are more complex than many researchers expected, suggesting that there are multiple cancer cell populations that need to be controlled, and therefore innovative treatment strategies will be required to substantially prolong patient lives.
“There is not a single targeted therapy out there in advanced cancers that induces responses for much more than a year,” said Dr. Engelman, Director of the Center for Thoracic Cancers at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School. “Yet the oncology community talks about targeted agents as tremendous successes because well-selected patients do better on these agents than on standard chemotherapy. But even in lung cancer patients who have an EGFR mutation, at nine months half of them have progressed. And this is true for BRAF-mutant melanomas, EML4-ALK lung cancers, and HER2-amplified breast cancers.
“So the idea is coming clear that as we've opened up this one door and have seen these very nice responses to targeted therapies…there are about 10 more doors ahead of us that stand in our way of making this a real transformation for patients, where they can get years or decades of benefit from these therapies.
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