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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 great majority of penile carcinomas diagnosed in Europe and the United States are of a nonbasaloid, nonwarty histological type. At present, an etiological relationship with HPV seems most plausible for penile carcinomas of the basaloid or warty subtypes; the precursor lesion is likely to be carcinoma in situ. In contrast, the precursor lesion for keratinizing SCC or verrucous carcinoma of the penis is not well established. Moreover, a further assessment of BXO in the absence of phimosis, or after circumcision, is needed to determine its role as an independent risk factor for the development of invasive penile cancer. It is also becoming clear that the mere presence of HPV is insufficient to have prognostic implications. Demonstration of HPV-mediated alterations in signaling pathways appears to be necessary. Currently, detection of elevated p16 expression appears to be a potential biomarker of HPV-mediated Rb inactivation in penile SCC.

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.

New tumor entities have been described, which are characteristic for children or young adults. The predominance of translocation carcinomas in the first decades of life demonstrates that renal cell carcinomas in young patients contain genetically and phenotypically distinct tumors with further potential for novel renal cell carcinoma subtypes. The far lower frequency of clear cell carcinomas with alterations in childhood compared to adults suggests that renal cell carcinomas in young patients have a unique genetic background.

Other tumors with apparent predilection for young age groups include clear cell carcinomas in the context of von Hippel-Lindau disease, carcinomas in combination with nephroblastomas, and renal cell carcinomas associated with neuroblastomas.

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.