Inhibition of Myc Gene Shows Promise Against Cancer

New research from a mouse study at UCSF shows that therapies that block action of a gene called Myc may prove useful in fighting cancer. The findings were reported online on August 17, 2008, in Nature. Corresponding author Gerard Evan, PhD, of UCSF says, “These data should spur renewed interest in Myc as a cancer target and, because Myc is involved in most human cancers, renew optimism that inhibiting Myc might be a safe and specific way of treating many different cancers.” Myc is a regulatory gene found in normal, healthy cells. However, it is commonly overexpressed in tumors, making it a possible target for anticancer therapies. Existing anticancer drugs target only a limited repertoire of cancer molecules, so the current study set out to determine which cancer molecules would make the best targets for inhibiting drugs, triggering regression of tumors with minimal side effects. Researcher Evan explains, “The Myc protein is a central engine of cell replication common to all cancer cells. But no drugs yet exist that inhibit Myc, in part because no one yet knows how to make such a drug, and in part because the likely side effects of blocking such a crucial engine were deemed too severe because the gene is needed for regenerative tissues like skin, bone marrow and intestine to replenish themselves.” The researchers built a genetic model in the mouse that mimics what an Myc-inhibiting drug would do to an especially virulent form of lung cancer. The study showed that Myc inhibition triggers rapid regression of early and established lung tumors, clearing the lungs in only a few days. At the same time, the side effects of inhibiting Myc on normal tissues were unexpectedly mild, well tolerated and completely reversible. Evan says that it was completely unexpected that inhibiting Myc would trigger such rapid regression of lung cancers, yet have so little toxicity for normal, proliferating tissues. Evan is Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research at UCSF and co-leader of the Cell Cycling and Signaling Program at UCSF Helen Diller Family Comprehensive Cancer Center. The study was supported by a grant from the National Cancer Institute. Study co-investigators were Laura Soucek, PhD, Jonathan Whitfield, PhD, Carla P. Martins, PhD, Andrew J. Finch, PhD, Daniel J. Murphy, PhD, Nicole M. Sodir, PhD, Anthony N. Karnezis, MD, PhD, and Lamorna Brown Swigart, PhD, all of UCSF’s Department of Pathology and Helen Diller Family Comprehensive Cancer Center; and Sergio Nasi of Istituto di Biologia e Patologia Molecolari, University La Sapienza, Rome, Italy.