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Over the last two decades, research into prostate cancer has accelerated at a great pace. Prostate cancer development and progression is an evolving process, involving complex interactions among cancer cells, their microenvironment, and genes affecting growth and metastasis.

Much research has been based on the androgen receptor and cell survival pathways associated with hormone resistance. Several molecular abnormalities have been identified, leading the way for the development of new combination targeted treatments. The development of micro-array expression analysis should hasten the identification of further diagnostic and prognostic markers and therapeutic targets. A better understanding of the biology of prostate cancer will also enable us to improve hormonal and chemotherapy options.

Prostate cancer is one of the common cancers where there is good evidence for a larger genetic component to its etiology, but the genetic models are complex. It is highly likely that the PCa predisposition genes will be polygenic and may be interacting within families. Some PCa predisposition genes are likely to be DNA repair genes (e.g., ) but these may account for only a small proportion of young cases. However, the discovery of high-risk mutations has led to the first clinical targeted screening trial based on genotype in this disease (the IMPACT study, discussed above), and this trial will serve as a basis for further targeted screening and chemoprevention trials based on genotype as further genes are identified. The lessons learned in IMPACT will be screening uptake in a high-risk male population, the psychological issues of screening men at higher risk of PCa, the utility of PSA in a higher risk population, the identification of new and better biomarkers and the clinical parameters of PCa so identified.

The dilemmas surrounding the value of screening and treatment in clinically localized prostate cancer remain unresolved. Recently published work from Scandinavia sheds some light into potential benefits of radical prostatectomy in preventing patients from dying from prostate cancer, although aggressive treatment did not improve overall survival compared with watchful waiting. Results from the now-merged ERSPC in Europe and PLCO in the U.S., the Protect study in the U.K., and the PIVOT study in the U.S. are awaited eagerly. It is reassuring for the medical community and prostate cancer patients worldwide that these long-standing dilemmas in the management of prostate are being resolved through large and robust randomized controlled trials supported by governments and funding institutions in Europe and the U.S.

The main limiting factors for the development of an effective gene therapy are efficiency of gene transfer, selectivity of tumor targeting, and the immunogenic properties of the vectors as well as general safety considerations. The findings of the early clinical trials of gene therapy have been promising, and results of several ongoing clinical trials are awaited. More recent trials have focused on combining gene therapy with conventional hormonal, chemotherapeutic, and radiation strategies in an attempt to overcome such problems as cellular heterogeneity and tumor resistance.

The expanding field of genomics provides an exciting new resource for the design of prostate-specific gene therapy strategies. The obstacles to the development of gene-based human therapeutics are significant but the rewards are great. Recent developments in molecular biology and virus delivery together with the ability to individualize molecular profiles point to a promising future for gene therapy for prostate cancer.

Current evidence suggests that radiotherapy is as effective as other curative modalities for prostate cancer. As well as the need for more mature data from high-dose, conformal studies, the ongoing randomized trials will better define its role. The optimum duration of hormone therapy is still unclear, and the patient population that most benefits from combined hormone therapy plus radiotherapy needs to be better defined. The next 5 to 10 years will yield some important data in clarifying these and other issues.

There is increasing evidence both in localized and in advanced disease that treatment has a beneficial effect on survival. But two questions remain: First, what proportion of men will benefit, and for how many men will treatment be unnecessary? Second, to what extent does the burden of treatment-related toxicity outweigh any survival benefit? Future research should be directed at identification of aggressive tumors in patients likely to benefit from treatment, and developing treatments with reduced toxicity.

Excellent cancer control and quality of life outcomes can be achieved by radical prostatectomy. The key, historical developments emphasize the importance of early diagnosis and consistency in surgical technique. Radical prostatectomy can be carried out by a variety of surgical approaches, and each has advantages and disadvantages. Technological development and application will increasingly influence future surgical practice by improving discrimination of those early-stage tumors that require definitive treatment and more consistently limiting treatment-related morbidity. The results of ongoing randomized controlled trials will add to the evidence base supporting the role of this important treatment option for the many men diagnosed with localized prostate cancer.

Over the years the treatment of prostate cancer has certainly become more humane. The most significant area of interest in this disease remains the exploration of the molecular basis for response and relapse. In understanding this, our hope is to provide more effective treatment for prostate cancer.

Chemotherapy in prostate cancer is an established treatment only for symptomatic hormone-refractory disease, where it can improve symptoms and quality of life but does not impact overall survival. Its role in earlier stage disease is currently being evaluated. Certainly, advancing chemotherapy may eliminate hormone-resistant clones early, thereby slowing the natural progression of this disease. Of the various cytotoxic agents currently under study, the taxanes show the most promise, combining encouraging PSA response rates with tolerability. Targeted therapies both alone or in combination may also prove effective, especially as we gain insight into prostate cancer at the molecular level and learn how best to use these agents. Phase III well-controlled clinical trials of the most promising regimens will then be needed to define the best regimens available.

If the major areas of prostate cancer research needing further development are discovering new targets for therapy, a better understanding of prostate cancer development, and discovery of new markers for more accurate diagnosis of prostate disease, then proteomic studies can contribute hugely to these areas. The relevance of protein rather than DNA and RNA information to such studies is that protein activity is the machinery of cell action; therefore, changes in protein profiles in cancer can be used on many levels, to detect, to understand, and finally to treat the cancer.