For persons with advanced non-small cell lung cancer (NSCLC), treatment often consists of a chemotherapy combination that contains platinum (the drugs cisplatin or carboplatin). While this treatment may prolong survival time and control the symptoms of disease, new types of treatment are being investigated. One area of promise for the treatment of many types of cancer, including NSCLC, is gene therapy. Researchers at US Oncology and Baylor University Medical Center now report that the injection of healthy p53 genes into cancer cells that have abnormal p53 genes achieves treatment responses in some persons with NSCLC.
Non-small cell lung cancer is a term used to describe at least 3 types of lung cancer, including epidermoid or squamous carcinoma, adenocarcinoma, and large cell carcinoma. NSCLC may be treated with surgery, radiation therapy, and/or chemotherapy. However, 1 of the reasons NSCLC may not respond to these treatments is that the NSCLC cells have an abnormal p53 gene. When normal, the p53 gene controls cell functioning. When abnormal (or mutated), this gene cannot perform its job properly and cancer cells develop and multiply uncontrollably. The identification of the abnormal p53 gene in NSCLC cells has led researchers to consider the benefits of gene therapy for persons with this type of cancer.
In this study, researchers developed a technique to inject normal p53 genes into the cancer cells, to see whether the normal genes would take over production of the abnormal cancer cells. To enable the cancer cells to accept the normal gene, the researchers inserted the normal p53 gene into a virus, called an adenovirus. The adenovirus is a large virus, responsible for many respiratory conditions, including the common cold, which is readily taken in by cells in the respiratory system. After placing the normal p53 gene into the adenovirus (referred to as Ad p53), researchers injected it into the cancer cells of persons with NSCLC.
The researchers treated 24 persons with NSCLC that either could not be removed with surgery or that had been resistant to previous treatments. The patients received 6 courses of chemotherapy with cisplatin; each chemotherapy course was followed 4 days later with an injections of Ad p53, directly into the cancer cells. The major side effect of the Ad p53 injection was fever. The results of the treatment showed a partial response in 2 persons, and stabilization of the cancer (no progression or worsening) in 17 persons. Laboratory tests showed that the cancer cells were being killed. Another observation was that, cancer cells that were not injected did continue to grow, while cancer cells in the same patient that were not injected responded to treatment.
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This study was the first of many that will investigate the use of gene therapy to treat NSCLC and other cancers. The findings show that the NSCLC cells respond to this type of gene therapy. In a second study, these researchers will attempt to treat NSCLC by infusing Ad p53 into the vein, rather than directly into the cancer cells, to determine whether this approach may be more effective. Persons who have advanced NSCLC may wish to talk with their doctor about the risks and benefits of participating in a clinical trial in which gene therapy or other new treatments are being studied. Other sources of information on ongoing clinical trials include a comprehensive, easy-to-use service provided by the National Cancer Institute (cancer.gov) and the Clinical Trials section and service offered by CancerConsultants.com (www.411cancer.com). (Journal of Clinical Oncology, Vol 18, No 3, pp 609-622, 2000)
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