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Old 08-25-2008, 10:12 AM
Dross Dross is offline
Join Date: Nov 2006
Posts: 883
Default CSHL scientists identify new drug target against virulent type of breast cancer

A new story entry has been added:

CSHL scientists identify new drug target against virulent type of breast cancer

The enzyme target, Brk, is shown to be an accelerator of HER2-positive tumors Tumor cells in a particular subset of breast cancer patients churn out too much of a protein called ErbB2 -- also often called HER2 -- which drives the cells to proliferate unchecked. Patients unlucky enough to be in this group -- about one in four -- have poorer prognoses and clinical outcomes than those who don't.
The drugs Herceptin and Lapatinib, prescribed in combination with other chemotherapeutic agents, have improved this picture significantly, but leave plenty of room for improvement: they suppress ErbB2 but are effective against less than half of ErbB2-producing tumors. Moreover, patients with tumors that do respond usually develop resistance to these drugs.
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Old 08-25-2008, 12:34 PM
gdpawel gdpawel is offline
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,360
Default Receptor and Enzyme Identification

Targeted drugs are based on a variety of biological mechanisms (pathways) that essentially stop cancer from spreading. They interfere with specific molecules (receptors and enzymes inside and outside a cancer cell) involved in carcinogenesis (the process by which normal cells become cancer cells) and tumor growth.

The most common targets on the outside of a cancer cell are receptors, which are proteins that help relay chemical messages. Many targets on the inside of a cell are enzymes, which are proteins that help speed up chemical reactions in the body.

By focusing on these molecular and cellular changes, targeted cancer drugs go after the "target" in these cells, rather than just all cells. In other words, they focus on molecular and cellular changes that are specific to cancer.

Because many cancer cells use similar pathways, the same drug could be used to treat one person's breast cancer and another person's lung cancer, as long as each tumor contained similar targets. This is why many of these treatments are being used in a variety of cancer types.

Although targeted therapy is appealing, it is more complex than meets the eye. Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes.

In other words, cancer cells have "backup systems" that allow them to survive. The result is that the drug does not shrink the tumor as expected. One approach to this problem is to target multiple pathways in a cancer cell.

There has been a continuous parade of new targeted small and large molecule therapies that will continue to be introduced into the market virtually blind. Most of them have been developed for use in solid tumors but some have also emerged for hematological malignancies. These targeted drugs mostly need to be combined with active chemotherapy to provide any benefit and the need for predictive tests for individualized therapy selection has increased.

Multi-targeted drugs can be well-predicted by measuring the effect of the drugs on the "function" (is the cell being killed regardless of the mechansim) of live cells, as opposed to a "target" (does the cell express a particular target the the drug is supposed to be attacking).

While a "target" assay tells you whether or not to give "one" drug, a "functional" assay can find other compounds and combinations and can recommend them from the one assay.

Functional profiling can discriminate between the activity of different “targeted” drugs and identify situations in which it is advantageous to combine the “targeted” drugs with other types of cancer drugs. Because these new “smart” drugs will work for “some” but not “all” cancer patients who receive them, functional profiling can accurately identify patients who would benefit from treatment with molecularly-targeted anti-cancer therapies.

The study of cell function analysis tells us that even when the disease is the same type, different patients' tumor respond differently to the same agents. A large molecule targeted drug may be more beneficial to some patients than a small molecule targeted drug (sometimes not).

Whatever the percentage of patients benefit from these drugs, the point is, targeted drugs are not for everybody. Pre-tests can help identify the individual cancer patient the drug works extremely well for, or it can tell that the drug is resistant. It is important to "personalize" cancer treatment, and this can be accomplished by testing the tumor first.

The ordinary trial system will not suffice if we are to encourage new drugs for restricted numbers of patients. More and more physicians and patients are turning to individualized therapies to treat cancers. Without individualized testing the efficacy of these drugs, it's difficult to determine which drugs are best for patients who don't respond to standard therapies.

Literature Citation:
Eur J Clin Invest 37 (suppl. 1):60, 2007
J Intern Med 2008; 264: 275-287

Last edited by gdpawel : 01-08-2009 at 02:27 AM. Reason: revise
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