Another area of active investigation is the mechanisms of metastatic progression. The malignant phenotype of a cancer cell is under both positive and negative controls but little is known about the genes that control metastasis. We have recently cloned a novel metastasis suppressor gene, KAI1, which may be important in prostate, breast, lung, and possibly other cancers. Further studies of this and related genes may yield important new insights into cancer diagnosis and treatment. In addition, molecular markers for the later stages of cancer progression may help define the environmental factors that influence malignant development.
Oxidative stress is a major form of endogenous and exogenous damage to cells.
A better understanding of the molecular mechanism of signal transduction leading to cell senescence or cell death through divergent pathways is required to understand cellular responses to environmental stresses, particularly oxidative damage. As cells progress to cancer, their responses to apoptotic signals change. Interestingly, cancer cells die at a higher rate than normal cells, suggesting that environmental modulators of apoptosis can influence the rate of tumor growth. One example of this is dietary restriction of animals, which reduces cancer progression by stimulating apoptosis of precancerous cells. We have shown that this is in part due to modulation by dietary restriction of circulating IGF1 levels, which blocks apoptosis of cancer cells.