MeetingsCancer: molecular players and unifying principles: The Keystone Symposium on the Molecular Basis of Cancer, Taos, NM, USA, 15–21 March 1999
Section snippets
Signaling and cancer
Ever since the discovery of the close links between tyrosine kinases and cancer, signal-transduction pathways have been of central interest to cancer researchers. This symposium was no exception. In one form or another, most of the talks dealt with signal transduction. An in-depth dissection of two important pathways was offered by Jean Wang (University of California at San Diego, CA, USA) and Joan Massague (Memorial Sloan Kettering Cancer Center, New York, NY, USA). Wang discussed the c-abl
Why p53?
The TP53 tumor suppressor gene, which encodes the p53 protein, is mutated in ∼50% of all human tumors, more than any other gene known to date. Excessive p53 activity can lead to growth arrest or apoptosis, in both cases sending the affected cell out of the replicative pool. Paradoxically, p53 activation is often coupled with growth-stimulatory pathways. p53 might thus serve as a safeguard against the uncontrolled activation of such pathways. One prediction of this model is that certain upstream
Genome integrity matters
Genomic instability is a key contributor to cancer progression. Various molecular aspects of genomic instability were addressed in the symposium. Richard Kolodner (Ludwig Institute, San Diego, CA, USA) reviewed the involvement of mismatch repair (MMR) genes in human cancer. Inactivation of such genes, occurring in many colorectal cancers, generates a ‘mutator’ phenotype. A yeast-based assay for mutator phenotype is now implicating additional genes in the maintenance of genome stability and
Protein stability: not just gene expression
In the early days of molecular biology, studies that explored the quantitative control of a particular protein intuitively centered on the regulation of its gene; not any more. The contribution of diverse post-transcriptional and often post-translational processes is now increasingly recognized, cancer being no exception. Karen Vousden (NCI, Frederick, MD, USA) discussed the regulation of p53 protein stability. A key player in this process is the Mdm2 protein, which binds p53 and targets it for
Cancer outside the culture dish
Rapid progress in understanding the molecular basis of cancer has been made possible largely through the availability of simple, convenient tissue culture systems. However, simplified tissue culture models have severe limitations, as was pointed out by Mina Bissel (Lawrence Berkeley National Laboratory, CA, USA). Several speakers provided compelling examples of answers that can only be obtained in whole animals. Thea Tlsty (University of California at San Francisco, CA, USA) reported that
Anticancer drugs: still a long way to go
At the end of the day, extensive understanding of the molecular basis of cancer should give rise to better cancer therapy. Scott Lowe (Cold Spring Harbor Laboratory, NY, USA) described the role of p53 in tumor killing by conventional chemotherapy. Loss of p53 function confers increased resistance to the apoptotic action of various DNA-damaging, anticancer drugs. Surprisingly, loss of ARF also has a partial protective effect, challenging the simple notion that ARF plays no role in activation of
Concluding remarks
The last decade has been characterized by amazingly rapid progress in understanding the molecular basis of cancer. Not everything has been satisfactorily resolved; however, basic principles are mostly becoming clear, providing clues to novel concepts in cancer therapy. The challenge for the first decades of the next millennium is to turn these concepts into real therapies, to reduce the current high rates of cancer mortality.
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