WHO IS MOST AT RISK?

Research activities of the PCI will be targeted in a way which enhances the assessment/advice, treatment and continuing care for men with prostate cancer and their families.

Research will target specific research issues which can be directly related to improved patient outcomes. For instance, specific research into prostate cancer will deal with the genetic aspects of the disease, psychosocial issues, the role of support groups and specific ways in which efficacy of surgery, radiotherapy and systemic therapies can be improved.

In particular, new therapeutic approaches will be developed and tested to complement existing therapies. Targeted alpha therapy clinical trials are scheduled for 2005. An important area of research/education will be to find better ways of preventing side effects, or dealing more effectively with side effects should they occur.

Research – Genetic Basis of Prostate Cancer

It has long been recognised that the risk of developing Prostate Cancer increases if a man has affected relatives. This increased risk is partly due to the genes that affected family members share by virtue of their common ancestry or genetic inheritance. The high incidence of Prostate Cancer in some of these affected families also indicates that some Prostate Cancer genes can play a dominant role in the disease.

When researchers at the Prostate Cancer Institute identified an Australian family with 4 of 5 brothers affected they immediately recognised the potential for this family to help identify gene(s) involved in Prostate Cancer. Dr Raymond Clarke Head of Cancer Genetics Research at the Institute planned a sophisticated analysis of this family's blood in search of the genes involved.

Dr Clarke explains how international research into Prostate Cancer has identified different stages of disease development and progression, however, no one has yet identified a unifying theme between those factors involved in the initiation of the cancer and the sequential steps of disease progression. While much has been learned concerning prostate biology little is known about the genetic and biochemical factors involved in the initiation and progression of Prostate Cancer.

The prostate is a small organ present in males only. The prostate is located between the bladder and the penis and provides important components of the semen. The hormone testosterone (Androgen) is essential for the growth, differentiation and secretory function of the prostate. In fact, both the normal prostate and early prostate cancer require testosterone for growth. The removal of testosterone actually prevents cancer growth in 80% of patients which contrasts with the growth of any recurrent cancer which is independent of testosterone. The testosterone (Androgen) hormone acts through another molecule known as the Androgen Receptor located within prostate cells.

Many studies have investigated the Androgen Receptor to determine its role in Prostate Cancer. While recapitulating the established role for testosterone in early prostate cancer growth previous research has indicated no direct link between the Androgen Receptor gene and increased risks of Prostate Cancer. More recently, however, our gene expression studies have identified an indirect linkage of the Androgen Receptor in familial prostate cancer.

Professor Kearsley, Institute Director, said "both good scientific method and good fortune returned results that surpassed all expectations." What is reassuring about our research into this exceptional prostate cancer family is that the genes we have identified can be implicated with many of the progressive steps involved in prostate cancer development. By implicating the Androgen Receptor in Prostate Cancer a unifying theme has begun to emerge linking many of the different aspects of Prostate Cancer Initiation and Development; starting with the requirement for the Androgen receptor in normal prostate biology to overlap with other essential progressive elements including DNA mutation, gene linkage, gene expression, tumour initiation and tumour growth (Figure 1).


(Figure 1)   Progressive Steps of Prostate Cancer   

     


Figure B      Family Gene Expression Profile


Dr Clarke said "this study was free of scientific and human bias because it was a global study where we did not investigate a set of 'favourite genes'. We did not know which genes were tested until the study was completed. Only 3 of 20,000 genes satisfied the strictest selection criteria. To our amazement - 2 of the 3 genes are associated with the Androgen Receptor while the third gene is a tumour suppressor.

The research is now focused on determining how these Prostate Cancer genes can be used to identify men at risk before they develop Prostate Cancer.