Eleventh annual Sapporo Cancer Seminar. Connecting the dots: assembling the pathways that control cell division.

The challenges that face cancer research continue to be frighteningly difficult. As more knowledge of the fundamental changes that promote cancer has come to light, the problem of how tumors develop has become clearer. Yet this new resolution not only tells us new information that advances our understand ing but also often tells us how little we actually know. At each stage, it would have been difficult to imagine how imprecise our view of the carcinogenic process was: not one oncogene, but many; not just positive regulation, but negative as well; multiple changes to promote each tumor; no required order for the multiple changes; different changes leading to apparently indistinguishable tumors. This field has moved from one more difficult realization to another. Yet standing in these difficult realizations are the most astonishing discoveries. The patterns laid down in determining the causes of human cancer have become the paradigm for the molecular signaling. The signaling processes that tell a cell when it is appropriate to divide are analogous to the signals that determine most, or perhaps all, molecular switches. As such, the difficult tasks of assembling these pathways hold enormous potential for all fields of biology. All meetings on the basic causes of cancer ultimately rest on this goal, assemble the normal signaling pathways, and hope fully uncover the pathology of the cancerous ones. Obviously, the decision of a cell to divide depends on its ability to interpret extracellular signals. These signals are transduced by poorly understood pathways and allow the cell either to divide or not. The signals are both positive and negative, yet little is known of whether the decision rests on a balance of these signals or whether there is a master switch that determines the priorities of the multiple signals. One of the most pressing tasks facing oncologists is to assemble these pathways. Uncovering the plot of this play has been slow. Identify the characters, try to decipher their lines, learn their motivations and their partners, piece together small scenes, and perhaps eventually enjoy the whole show. This report covers one small assembly of wouldbe playwrights, experimenting with their small scenes. The subject of the 1991 Sapporo Cancer Seminar was "Molecules in Carcinogenic Processes."