Frontiers in prostate cancer. Telomeres and chaos

New frontiers are emerging in our understanding of the biology of prostate cancer. Four topics are addressed in this article. The first topic addressed is the search for candidate genes for cancer susceptibility that are related to familial forms of prostate cancer. Second, the demonstration of a correlation between prostate cancer, shortened telomere lengths, and the appearance of telomerase activity as well as related findings regarding cellular senescence and immortalilty are presented. Third, epigenetic aspects of tumorigenesis, in particular, the recognition that cancer‐related genes only function within the context of certain cell types, are discussed. This tissue specificity is dictated, in part, by the cell matrix structures that serve to hard wire the interaction of the DNA with the external environment. Fourth, concepts recently developed in the fields of complexity and chaos theory are discussed that may offer a better understanding of the fundamental changes in tumor cell morphology and heterogeneity, which are hallmarks of the cancer state. Specifically, the authors discuss the concept that dynamic attractors may dictate the three‐dimensional organization of the DNA within the nucleus through interactions with the nuclear matrix. The nuclear matrix is a dynamic scaffolding structure, which temporally and spatially organizes the genome and plays a major role in determining tissue specificity. The authors believe that the new principles and concepts presented in this article will provide additional insight into prostate cancer as well as potential foci for future therapeutic interventions. Cancer 1995;75:2027–35.