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Return to Novel Approach To Brain Cancer Personalizes Treatment Overview

More on Novel Approach To Brain Cancer Personalizes Treatment

Novel Approach To Brain Cancer Personalizes Treatment

NEW YORK (Apr 21, 2014)

In a novel approach to the treatment of brain cancer, doctors are designing and testing therapies for clinical trials one patient at a time. This personalized approach to medicine may offer hope to patients afflicted with glioblastomas (GBMs), the most common and aggressive type of primary brain tumor with an average survival of one to 2 years.

"Rather than a 'one size fits all' or a 'one size doesn't fit anyone' approach, I think the future lies in a 'one size fits one' strategy, identifying the molecular drivers of an individual patient's tumor in order to personalize treatment," said Andrew B. Lassman, M.D. "To do this, every patient, if possible, would undergo detailed molecular analysis of resected tumor tissue for the molecular and genetic underpinnings."

Andrew B. Lassman, M.D.
Andrew B. Lassman, M.D.

Current treatments for GBMs are not particularly effective and can be toxic, noted Dr. Lassman. However, doctors are beginning to understand the underlying biology that causes GBMs. By adapting lessons learned from other tumor types, Dr. Lassman's group is working to develop more precise treatments for the various subtypes of GBM. "For example, non-small cell lung cancer has been differentiated into at least 12 molecular subtypes and molecularly-oriented therapies have been designed and are effective for some of those subtypes," said Dr. Lassman.

Clinical trials that incorporate molecular eligibility criteria are already underway. "We have multiple clinical trials in our portfolio for brain tumors based on a new paradigm that restricts eligibility to those patients most likely to benefit," said Dr. Lassman. "To no surprise, those less selective trials were unsuccessful," he added.

Andrea Califano, Ph.D.
Andrea Califano, Ph.D.

The work of Dr. Lassman's team is largely informed by research led by Andrea Califano, Ph.D., who is pursuing a novel approach to cancer clinical trials in which therapies are designed and tested one patient at a time. "A drug may kill 90% to 99% of the tumor cells, but the remaining one percent may eventually kill the patient because they were not sensitive to the drug – whatever the reason. To address this problem, we are trying to understand how each patient's tumor is regulated."

Dr. Califano and his group developed a novel method to identify genes and gene pairs that are critical for the survival of the tumor, but are not critical for normal cells. "We reverse engineer the patient's tumor, much as you would an unknown piece of machinery that no longer works properly," said Dr. Califano.

After the investigators identify the individual patient's tumor mechanism, they test appropriate FDA-approved drugs, first in laboratory cultures and then in a mouse model that closely matches the patient's tumor. Drugs that are effective in the mouse model, individually or in combination, would then be considered as a therapeutic option for the patient.

Currently, Dr. Califano's team is awaiting IRB approval to evaluate the approach on a larger scale. The researchers expect that other patients whose tumors have the same master regulators could be treated with the same drug, extending the benefits from one patient to many.

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