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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.

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 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.

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.

This chapter has summarized the large amount of experimental work exploring the potential for gene therapy in bladder cancer. Several phase I trials have now been reported, and the next decade holds out the hope of successful transfer of these therapies to the clinical situation. The future must lie with multimodality treatment, and the studies that have described synergy between chemotherapy and gene therapy are extremely encouraging. However, there is a long way to go, and, unfortunately, achieving efficacious therapy is not the only challenge, because gene therapy continues to court ethical controversy, and its success is most likely to depend on its acceptance by the general public.

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.

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.

The last 30 years has seen a revolution in the chemotherapy treatment of germ cell cancer, and the vast majority of patients with metastatic disease can now expect to be cured. Worldwide, BEP remains the gold standard chemotherapy treatment for all groups of patients presenting with metastatic germ cell cancer. For patients presenting with good prognosis metastatic disease, cure rates now approach 98% and the research focus has switched from improving outcome to reducing treatment-related morbidity. For patients with intermediate and poor prognosis metastatic disease, further improvements in treatment outcomes remain a research priority through the use of novel agents or the safe delivery of dose-intensified treatments. In the adjuvant setting, short-course BEP has established itself as a treatment option for high-risk stage I nonseminoma; for seminoma, the use of single-agent carboplatin seems likely to replace para-aortic nodal strip radiotherapy as the standard adjuvant treatment for stage I disease. The long-term morbidities of BEP chemotherapy are now more clearly defined and allow for an informed discussion with patients about to embark on chemotherapy and appropriate surveillance of individuals thereafter. It would be optimistic to predict that the next 30 years will yield as many advances in the treatment of this disease as have been witnessed since the mid-1970s; however, with our ever-increasing understanding about the natural history and biology of this disease, we should remain determined in our efforts to maximize cure and minimize morbidity in all patients presenting with germ cell cancer.

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.

The last 30 years has seen a revolution in the chemotherapy treatment of germ cell cancer, and the vast majority of patients with metastatic disease can now expect to be cured. Worldwide, BEP remains the gold standard chemotherapy treatment for all groups of patients presenting with metastatic germ cell cancer. For patients presenting with good prognosis metastatic disease, cure rates now approach 98% and the research focus has switched from improving outcome to reducing treatment-related morbidity. For patients with intermediate and poor prognosis metastatic disease, further improvements in treatment outcomes remain a research priority through the use of novel agents or the safe delivery of dose-intensified treatments. In the adjuvant setting, short-course BEP has established itself as a treatment option for high-risk stage I nonseminoma; for seminoma, the use of single-agent carboplatin seems likely to replace para-aortic nodal strip radiotherapy as the standard adjuvant treatment for stage I disease. The long-term morbidities of BEP chemotherapy are now more clearly defined and allow for an informed discussion with patients about to embark on chemotherapy and appropriate surveillance of individuals thereafter. It would be optimistic to predict that the next 30 years will yield as many advances in the treatment of this disease as have been witnessed since the mid-1970s; however, with our ever-increasing understanding about the natural history and biology of this disease, we should remain determined in our efforts to maximize cure and minimize morbidity in all patients presenting with germ cell cancer.