One standard approach to curing cancer is to kill off malignant cells, and doctors consider their treatment a success when no cancerous cells remain. However, many patients whose test results show no malignancy have their cancer reappear years later. New research suggests an explanation.
Scientists working with mice find that when they crank up production of a protein called Myc, they spur liver-tumor growth, and stopping Myc manufacture halts it. Although the cancer then regresses, not all the tumor cells die, the researchers find. Some differentiate into what appear to be normal liver cells. But their cancerous proclivity reawakens when the cells are given the right cue—a new jolt of Myc, the researchers report in an upcoming Nature.
A dormant cancer might not be so bad, says study coauthor Dean W. Felsher of Stanford University School of Medicine. "If we can make cancer sleep for a lifetime, maybe that's good enough," he says.
Myc is a much-studied protein because it turns on or off many genes that influence cell replication. Past research suggested that Myc might orchestrate the shadowy changes by which a normal cell becomes malignant.
To test the protein's effects, Felsher and his colleagues genetically engineered mice to make excess Myc in their liver cells. The new genetic trait also shut down Myc production in the presence of a common antibiotic.
The mice grew up healthy when given a steady supply of the antibiotic. But when the drug was withdrawn, all the mice developed aggressive liver cancer during the next 12 weeks or so. Tests revealed high concentrations of Myc in the tumors.
When the mice were again started on the antibiotic, all showed a sharp decrease in Myc and rapid tumor shrinkage.
Further tests revealed that some tumor cells deprived of excess Myc reverted to looking and behaving as normal liver cells do, without signs of aberrant growth.
Scientists haven't known why tumors reappear in many patients who had seemed free of their earlier cancer, says Nelson Fausto of the University of Washington School of Medicine in Seattle. Therefore, the evidence of a dormant malignancy is "an extremely interesting finding," he says.
Because Myc activates a host of genes involved in cell replication, it could be considered "an Achilles' heel of cancer," says Francesco Feo of the University of Sassari in Italy. Scientists are pursuing various strategies for neutralizing Myc, but most are in the early stages of research, he says.
"There's no doubt that [Myc] is a very important target," says David L. Levens of the National Cancer Institute in Bethesda, Md.
But Myc participates in several essential functions, so shutting down its production may be too disruptive to healthy cells. Moreover, Feo cautions that cancer cells often compensate for the loss of a protein.
University of Washington
School of Medicine
Seattle, WA 98195
Dean W. Felsher
Stanford University School of Medicine
269 Campus Drive
Stanford, CA 94305-5151
Department of Biomedical Science
Division of Experimental Pathology and Oncology
University of Sassari
Via P. Manzella, 4
David L. Levens
Laboratory of Pathology
National Cancer Institute, CCR
Building 10, Room 2N106
Bethesda, MD 20892-1500
Levens, D. 2002. Disentangling the MYC web. Proceedings of the National Academy of Sciences 99(April 30):5757-5759. Available at [Go to].
Menssen, A., and H. Hermeking. 2002. Characterization of the c-MYC-regulated transcriptome by SAGE: Identification and analysis of c-MYC target genes. Proceedings of the National Academy of Sciences 99(April 30):6274-6279. Available at [Go to].
Simile, M.M. . . . F. Feo, et al. 2004. Downregulation of c-myc and Cyclin D1 genes by antisense oligodeoxy nucleotides inhibits the expression of e2F1 and in vitro growth of HepG2 and Morris 5123 liver cancer cells. Carcinogenesis 25(March):333-341. Abstract available at [Go to].
Uhr, J., et al. 1997. Cancer dormancy: Opportunities for new therapeutic approaches. Nature Medicine 3(May):505-509.
For further information about the myc protein, go to [Go to].