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Chemotherapy Resistance


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Chemotherapy resistance is the major cause of cancer treatment failure. Breast, prostate, and ovarian cancers represent malignancies in which the development of drug-resistant forms has prevented significant cures with current conventional chemotherapeutic agents. A high degree of drug resistance is also associated with cancers of the liver, colon, pancreas, kidney, and lung. Even today, 90 percent of all drug cures occur in only 10 percent of cancer types that are intrinsically drug-sensitive, e.g., acute childhood leukemia, testicular cancer, and Hodgkin's disease. Although modest inroads continue to be made in the treatment and understanding of chemotherapy refractory cancers (cancer that progresses during treatment or recur within six months of treatment), a therapeutic approach to drug resistance is urgently needed. Using human breast cancer cells as a model, they have discovered a biological process responsible for resistance to adriamycin, the most widely employed anti-cancer drug in the world, and the main drug to which breast tumors become resistant. In the realm of therapy, knowledge of this biological process has allowed scientists to incorporate relatively nontoxic, clinically available drugs that act to block adriamycin resistance, effectively "chemosensitizing" otherwise resistant tumors. Discovery of this drug-resistance pathway has also uncovered a marker that will be tested in breast cancer patients and evaluated as a predictor of response to chemotherapy. As they have identified the gene responsible for some forms of chemotherapy resistance, their aims are geared toward gene therapy employed to incapacitate the resistance mechanism. Having recently found similar resistance patterns in prostate and ovarian malignancies indicates that they can apply a like approach to combat chemotherapy resistance in other gender-specific cancers. Some tumors (like adenocarcinoma) are highly resistant to virtually all anti-cancer drugs, while other tumors are quite sensitive. Most patient tumors fall in between these two extremes, with resistance to some drugs but not to others. Many mechanisms by which cancer cells develop resistance have been identified. Most cancers have some degree of drug resistance with many patients not responding to the chemotherapy most commonly prescribed for the tumor type. The chemotherapeutic drug Taxol is heavily used as a cocktail with Carboplatin. The effectiveness of this combination regimen is limited because ovarian cancer is ordinarily detected in its late stages (as lung and breast cancer can also) when most patients develop resistance to chemotherapy drugs. Virtually all cancers contain cells resistant to chemotherapy and the number of drug resistant cells increases expodentially as a tumor expands in size. After treatment is completed the surviving drug resistant cells often proliferate rapidly. The late stage of "recurrent ovarian cancer" makes the chemo combination of Taxol & Carboplatin drug resistent to cancer cells and suppressed the immune system, making it possible new tumors to grow because the patient has been rendered unable to resist them. Some side effects from chemotherapy may include anemia, infections, hair loss, and lung damage. In some cases, it can cause brain damage (leukoencephalopathy). Since both radiation and chemotherapy suppress the immune system, it is possible that new tumors are allowed to grow because the patient has been rendered unable to resist them. A person who is cured of cancer by these drastic means may find himself struggling with a new, drug-induced tumor a few years later. A malfunctioning immune system can fail to stop the growth of cancer cells. The results of years of clinical trials on patient populations are considered enough indication on how an individual will respond. The percentage of patients that must respond to a drug before it is approved varies from as "low" as 20% to as high as 80%, depending on the type of cancer. Thereafter it is used routinely for all patients with the same form of cancer, though unfortunately a drug that helps one person does not necessarily mean that it will help all people with the same diagnosis. The notion that patients treated by conventional therapies live longer than untreated victims is biased by the methods of defining the groups studied. If a person in the untreated category dies at any time while he or she is being studied, this is recorded as a death in the control group and registered as a failure of the no treatment approach. However, if patients in the treated category die during the course of treatment (before the course is completed), their cases are rejected from the data since these patients do not then meet the criteria established by definition of the term "treated". A patient dying on day 89 of a prescribed 90-day course of chemotherapy would be dropped from the list of treated patients.


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