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Whole Cell Profiling

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Subject: Predictive Tests For Targeted Drugs
Date: 09/20/2006
Cells are the most basic structure of the body. Cells make up tissues, and tissues make up organs, such as the lungs or liver. Each cell is surrounded by a membrane, a thin layer that separates the outside of the cell from the inside.


For a cell to perform necessary functions for the body and respond to its surroundings, it needs to communicate with other cells in the body. Communication occurs through chemical messages in a process called signal transduction. The purpose of these signals is to tell the cell what to do, such as when to grow, divide into two new cells, and die.


Targeted cancer therapies use drugs that block the growth and spread of cancer by interfering with specific molecules involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than current treatments and less harmful to normal cells.


Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, "small" molecules that act on multiple receptors in the cancerous cells, like Tyberb and Sutent. Targeted "small-molecule" therapies ruled at the recent annual ASCO meeting of oncologists. The trend is away from the monoclonals to the small molecules, a trend in which a new predictive test may be able to hasten.


The EGRFx (TM) assay is able to test molecularly-targeted anti-cancer drug therapies like Iressa, Tarceva, Tykerb, Sutent and possibly Nexavar, because of being small molecules. The EGFRx (TM) assay relies upon a technique known as Whole Cell Profiling, in which living tumor cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs.


A variety of metabolic and apoptotic measurements are then used to determine if a specific drug was successful at killing the patient's cancer cells. The whole cell profiling method differs from other tests in that it assesses the activity of a drug upon combined effect of all cellular processes, using several metabolic (cell metabolism) and morphologic (structure) endpoints, at the cell "population" level (rather than at the "single cell" level).


Other tests, such as those which identify DNA or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process. Whole Cell Profiling measures genes before and after drug exposure. Gene Expression Profiles measures the gene expression only in the "resting" state, prior to drug exposure.


Not only is this an important predictive test, it is also a unique tool that can help to identify newer and better drugs, evaluate promising drug combinations, and serve as a "gold standard" correlative model with which to develop new DNA, RNA, and protein-based tests that better predict for drug activity.


Laboratory screening of samples from a patient's tumor can help select the appropriate treatment to administer, avoiding ineffective drugs and sparing patients the side effects normally associated with these agents.


Under this approach, scientists study how an individual's cancerous cells respond to several drugs. Doctors have learned that even when the disease is the same type, different patients' tumors respond differently to chemotherapeutic drugs.


More and more physicians and patients are turning to individualized therapies to treat cancers. Without individualized testing, it's difficult to determine which drugs are best for patients who don't respond to standard therapies.


Assay-directed chemotherapy is an individualized approach to killing cancer. A method used to determine what precise medications would kill the particular cancer.


Doctors have assumed that stopping cell division would stop cancer, because most cancer cells divide and grow rapidly. But the approach didn't always kill the malignant cells. Cancer isn't a case of cells growing out of control, but of cells refusing to die on schedule.


Assay testing can provide predictive information to help physicians choose between chemotherapy drugs, eliminate potentially ineffective drugs from treatment regimens and assist in the formulation of an optimal therapy choice for each patient.


This can spare the patient from unnecessary toxicity associated with ineffective treatment and offers a better chance of tumor response resulting in progression-free survival.


Preponderance of currently-available evidence argues persuasively in favor of the use of the assays.

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  1. Whole Cell Profiling
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