Baltimore Sun Examines Genetic Resear...

Baltimore Sun Examines Genetic Research Technology Aimed At Tes...

There are 1 comment on the Pharma-lexicon.com story from Nov 9, 2006, titled Baltimore Sun Examines Genetic Research Technology Aimed At Tes.... In it, Pharma-lexicon.com reports that:

In the past, physicians were restricted to such factors as a patient's age, family history and tumor size in assessing cancer risk and treatment method, but that has changed as researchers "identify genes that, ...

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gdpawel

Franklin Park, NJ

#1 Dec 7, 2006
Combination Cellular And Gene-Based Testing

Cancer occurs when cells lose the molecular mechanisms that control their growth and death, resulting in uncontolled cell proliferation and form tumors. These molecular mechanisms are contolled by genes encoded in the DNA of the cell, and acquired mutations or other changes in these genes lead to loss of control. Therefore, cancers are genetic diseases. But, each individual tumor, even those of the same general type will have different mutations, the consequences of which may be altered by the tissue environment, which can in turn be influenced by the external environment. The result is that cancers are even more different from each other than the individuals affected.

This heterogeneity means that a particular drug will rarely be effective against all tumors of a particular type, and the degree of efficacy will vary between patients. Also, as a result of their original mutations, many tumor cells acquire the ability to adapt rapidly to changes in their environment, sometimes by further mutation, often by molecular changes which induce resistance to the drugs used to treat them. Further courses of chemotherapy then select for resistant cells, and the treatment eventually fails to control the tumor.

To overcome the problems of heterogeneity and prevent rapid cellular adaptation, oncologists are able to tailor chemotherapy to individual patients. This is done by testing the tumor cells to see if they are susceptible to particular drugs, before giving them to the patient. Many hope that molecular tests may hold the key to success, particularly as more specific drugs are designed to hit the molecular changes that are responsible for the uncontrolled growth of cancer cells. However, most tests that are now in use have limited predictive accuracy.

So how about exposing cancer cells to the drug and testing their effect? You need to expose the cancer cells to the drugs without altering their behavior from the original tumor. It is not possible to remove the non-cancer cells from the tumor without doing this. But certain assay culture methods can get rid of the non-cancer cells before the end of the culture period. These cell culture assays have contributed to the molecular understanding of chemosensitivity and resistance.

Cell culture assay tests with cell-death endpoints are effective in identifying gene expression patterns that correlate with clinical drug resistance. Gene expression definitions of sensitivity and resistance are significantly and independently associated with treatment outcome.

Cell culture assays are the Rosetta Stone which allows for identification of clinically relevant gene expression patterns which correlate with clinical drug resistance for different drugs in specific diseases. There is no single gene whose expression accurately predicts therapy outcome, emphasizing that cancer is a complex disease and needs to be attacked on many fronts.

A number of cell culture assay labs across the country have data from tens of thousands of fresh human tumor specimens, representing virtually all types of human solid and hematologic neoplasms. Cell culture assay labs have the Rosetta Stone database necessary to define sensitivity and resistance for virtually all of the currently available drugs in virtually all types of human solid and hematologic neoplasms.

I believe that improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing will offer predictive insight into the nature of an individual's particular cancer and enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different and the response to given drugs is very different.

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