Novel drug combo improves breast cancer survival

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SAN ANTONIO -- Some women with very advanced breast cancer may have a new treatment option. A combination of two drugs that more precisely target tumors significantly extended the lives of women who had stopped responding to other medicines, doctors reported Friday.

It was the first big test of combining Herceptin and Tykerb. In a study of 300 patients, women receiving both drugs lived nearly five months longer than those given Tykerb alone.

http://www.washingtonpost.com/wp-dyn...102496_pf.html

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Targeted therapies are typically not very effective when used singularly or even in combination with conventional chemotherapies. The targets of many of these drugs are so narrow that cancer cells are likely to eventually find ways to bypass them. Durable responses are rare and no one with advanced cancer has yet to be cured with targeted therapy. Physicians may have to combine several targeted treatments to try an achieve cures or durable responses.

So, some clinical studies are trying to delineate the benefit achieved when combining two innovative targeted treatments together. However, these targeted therapies produce limited results because they can help a relatively small subgroup of cancer patients, and tests to pinpoint those patients are desperately needed. The trick is figuring out which patients will respond. The challenge is to figure out which patients to give them to. There is a targeted assay to match targeted cancer therapies to those cancer patients.

The targeted assay uses "whole cell profiling" which is a variety of metabolic (cell metabolism) and morphologic (structure) measurements to determine if a specific drug is successful at killing the patient's cancer cells. Whole cell profiling measures genes before and after drug exposure. It makes the statistically significant association between prospectively reported test results and patient survival.

And it is the only cell-death endpoint assay system in which drug effect upon cancer cells is visualized directly. Photomicrographs of actual tumor cells show the condition of cells as they are received and enriched in the lab, and also the conditions of control cells post-culture. In this visualization, the microscopic slides sometime show that the exact same identical individual culture well, shows some clusters have taken up vast amounts of the molecular drug, while right next door, clusters of the same size, same appearance, same everything haven't taken up any of the drug.

It doesn't matter though if there is a target molecule (protein or receptor) in the cell that the targeted drug is going after. If the drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug resistance is multifactorial. The one advantage of whole cell profiling is that it can show this at the cell "population" level, measuring the interaction of the entire genome.

This could help solve the problem of knowing which patients can benefit from these molecular drugs. Afterall, these "smart" drugs do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.

Literature Citation: Weisenthal, LM, Patel, N, and Rueff-Weisenthal, C. Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood. J Intern Med 264:275-287, September 2008

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According to Dr. Arny Glazier, a cancer researcher, in his book Cure: Scientific, Social and Organizational Requirements for the Specific Cure of Cancer," the consistent and specific cure or control of cancer will require multiple drugs administered in combination targeted to abnormal patterns of normal cellular machinery that effect or reflect malignant behavior. Finding the 'patterns' of malignant cells and developing a set of 5 to10 drugs in order to cure or control cancer."

So the consistent and specific cure of cancer requires therapy that can target the set of "all" malignant cells that could evolve in the human body. It is thought that each anti-cancer drug needs to be given at a dose sufficient to kill cells that express the pattern targeted by the individual drug. In order to kill "all" patterns of malignant cells, you need to give full doses of all drugs (5-10) in combination.

However, it is not possible to give five to ten existing drugs together in combination, the toxicity would be prohibitive. They have overlapping toxicity, which means you need to cut the doses when you give them together, so you get down to homeopathic dose levels.

This could be overcomed with potentiation therapy (IPT) or low-dose chemotherapy, which makes cell membranes more permeable and increases uptake of drugs into cells. IPT selectively targets tumor cells, which usually have more insulin receptors than normal cells. Makes tumor cells more susceptible to chemo by modifying cell metabolism. As a result, cancer patients can greatly reduce chemo dosage (reduce it to only 10-15%), while at the same time, receive the 5-10 drugs in order to effectively cure or control cancer, and eliminate most side effects while increasing the effectiveness of chemo (chemo synthesizer).

Given the current state of the art, in vitro drug sensitivity testing could be of significant clinical value. Upgrading clinical therapy by using drug sensitivity assays measuring "cell death" of three dimensional microclusters of live "fresh" tumor cells, can improve the situation by allowing more drugs to be considered. The more drug types there are in the selective arsenal, the more likely the system is to prove beneficial.

Cell culture assays tests with cell-death endpoints are the Rosetta Stone which allows for identification of clinically relevant gene expression patterns which correlate with clinical drug resistance and sensitivity 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 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.

The consistent and specific cure or control of cancer will require developing a set of drugs, given in combination, targeted to patterns of normal cellular machinery related to proliferation and invasiveness. These requirements define a rational, practical strategy to develop curative therapy for all forms of solid cancer.

Source: http://www.lulu.com/content/276115