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Circulating tumor cells can reveal genetic signature of dangerous lung cancers

Massachusetts General Hospital (MGH) investigators have shown that an MGH-developed, microchip-based device that detects and analyzes tumor cells in the bloodstream can be used to determine the genetic signature of lung tumors, allowing identification of those appropriate for targeted treatment and monitoring genetic changes that occur during therapy. A pilot study of the device called the CTC-chip will appear in the July 24 New England Journal of Medicine and is receiving early online release.

http://www.medicalnewstoday.com/articles/113846.php

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The interest in and the knowledge of gene expression profiling in cancer medicine has heighten since the completion of the human genome project. However, researchers have cautioned the science of gene expression profiling, in which scientists examine the genetic signature of a cell.

The gene chip is a device that measures differences in gene sequence, gene expression or protein expression in biological samples. It may be used to compare gene or protein expression under different conditions, such as cells found in cancer.

Hence the headlong rush to develop tests to identify molecular predisposing mechansims whose presence still does not guarantee that a drug will be effective for an individual patient. Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class.

The challenge is to identify which patients the targeted treatment will be most effective. Tumors can become resistant to a targeted treatment, or the drug no longer works, even if it has previously been effective in shrinking a tumor. Drugs are combined with existing ones to target the tumor more effectively. Most cancers cannot be effectively treated with targeted drugs alone.

What is needed is to measure the net effect of all processes within the cancer, acting with and against each other in real time, and test living cells actually exposed to drugs and drug combinations of interest. The key to understanding the genome is understanding how cells work. How is the cell being killed regardless of the mechanism?

The core understanding is the cell, composed of hundreds of complex molecules that regulate the pathways necessary for vital cellular functions. If a targeted drug could perturb any of these pathways, it is important to examine the effects of drug combinations within the context of the cell. Both genomics and proeomics can identify potential therapeutic targets, but these targets require the determination of cellular endpoints.

Sources:

Eur J Clin Invest, Volume 37(suppl. 1):60, April 2007

BMJ 2007;334(suppl 1):s18 (6 January), doi:10.1136/bmj.39034.719942.94

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