PubMed · 7763162
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R J Marino. 1995. Statistical hypothesis testing.. https://doi.org/10.1016/s0003-9993(95)80518-4
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Gene-based therapies for cancer in clinical trials include strategies that involve augmentation of immunotherapeutic and chemotherapeutic approaches. These strategies include ex vivo and in vivo cytokine gene transfer, drug sensitization with genes for prodrug delivery, and the use of drug-resistance genes for bone marrow protection from high-dose chemotherapy. Inactivation of oncogene expression and gene replacement for tumor suppressor genes are among the strategies for targeting the underlying genetic lesions in the cancer cell. A review of clinical trial results to date, primarily in patients with very advanced cancers refractory to conventional treatments, indicates that these treatments can mediate tumor regression with acceptably low toxicity. Vector development remains a critical area for future research. Important areas for future research include modifying viral vectors to reduce toxicity and immunogenicity, increasing the transduction efficiency of nonviral vectors, enhancing vector targeting and specificity, regulating gene expression, and identifying synergies between gene-based agents and other cancer therapeutics.
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The current debate regarding early detection and aggressive treatment of prostate cancer is fueled by the absence of controlled studies defining the risks and benefits of prostate cancer screening, and by the lack of adequately powered trials demonstrating the benefit of curative treatment for early-stage prostate cancer. Pending the results of clinical trials in 10 to 15 years, advocates of early detection of prostate cancer with digital rectal examination and prostate-specific antigen have compared prostate cancer screening with the effective strategy of breast cancer screening, implying that prostate cancer screening should similarly reduce cancer mortality. They have also cited the high burden of disease, the acceptable operating characteristics of digital rectal examination and prostate-specific antigen, a stage shift among cases detected by screening, and the theoretical curability of early-stage disease as sufficient reasons to proceed with screening. These arguments, however, are reminiscent of earlier arguments in favor of lung cancer screening with chest x-ray examination and sputum cytology, a practice ultimately proven ineffective in clinical trials. We reviewed published articles on lung and prostate cancer screening and identified many parallels. While prostate cancer screening may one day prove effective, analogies between the current prostate cancer screening controversy and the older lung cancer screening debate should inject some caution regarding widespread dissemination of prostate cancer screening without experimental evidence that such screening does more good than harm.