Cancer results from mutations that alter the normal regulation of cell growth, differentiation, and death. Significant progress has been made understanding the complex interplay between genetic events, their effects on regulatory proteins, and the resulting changes in the malignant phenotype. There is optimism that this will lead to the development of novel cancer treatments that specifically target these alterations. However, fundamental research is largely based on model systems that ignore the complexity of human cancers. Single cell measurements using flow and image cytometry give an indication of cellular heterogeneity. Because cytometry allows simultaneous measurement of multiple parameters, it also has the potential to map regulatory pathways, and to define those critical abnormalities that determine biological aggression. However, there are problems to overcome before it could be used to study molecular mechanisms regulating cell growth and death in human cancers. Working symposia on human tumor heterogeneity were held at Kananaskis, Alberta, in May 1995 and 1996 to consider the practical steps needed to achieve this goal. These meetings focussed on the technical problems of quantifying multiple cytoplasmic or nuclear markers, using fluorescent probes for proteins and oligonucleotides. The problems of data analysis were also considered at length. Having refined the basic analytical tools needed, an enlarged meeting will be held at the University of Toronto in June 1997. The goal at this meeting is to develop an integrated approach for studying pathways that control the cell cycle and apoptosis in human cancers, using advanced cytometric techniques. Participation by pathologists and basic scientists will be actively encouraged. This proposal is for funds to provide travelling fellowships for young investigators.
