Blood assays for earlier detection of cancers

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A significant way to improve therapy against cancer is to detect cancer earlier than we can at present. Current methods are similar to trying to put out a fire after the house is in flames. Rather, we need to invent `smoke detector' techniques that signal very early cancer or the development of metastases. These would allow treatment of far fewer cancer cells, prior to extensive metastases and drug resistance. They should aid present treatments by surgery, radiation, chemotherapy and perhaps immunology and differentiation therapy.

Our goal is to devise early warning systems. We already have found many mRNAs whose expression is modified in cancers (Sager, 1997; Ford, 1998; Fournier, 1999a, b; Guan, 2000; Martin, 2000). We are now developing markers and methods to detect very low numbers of tumor cells that are released into blood early in the progression of solid tumors. Some of these markers are found in 3 ml blood samples from cancer patients, and are missing from blood of normal individuals.

To find new genes we apply the concept of Expression Genetics (Sager, 1997), using the differential display method (Pardee, 1999). We are analysing 200 differentially expressed mRNAs from breast cancers, applying high density membrane-based hybridization arrays. Cluster analysis identifies groups of genes whose expression patterns correlate with clinical information, including estrogen receptor status, tumor size, and stage (Martin, 2000). The early detection methods we are developing could also be applied to predict optimal cancer therapy, to determine therapeutic efficacy by measuring decreases of markers in blood, and to detect recurrence after therapy. These techniques could be applied to other body fluids.