Cell Cycling Research May Hold Key to Improving Cancer Therapy

SAN DIEGO--So little is known about cell cycling that a new study ona possible mechanism for why cells fail to exit the cell cycle was termedthe "most exciting presentation" of the American Associationfor Cancer Research's 88th annual meeting. Stephen H. Friend, MD, of theFred Hutchinson Cancer Research Center, made the comment at a press briefingheld at the meeting.

The research, from the Cell Biology and Metabolism Branch of the NIH'sNational Institute of Child Health and Human Development, led by NCI directorRichard Klausner, MD, involves the mechanism of action of the von Hippel-Lindau(VHL) tumor suppressor gene. The inactivation of this gene is associatedwith both von Hippel-Lindau disease and sporadic kidney cancer.

The NIH scientists, Arnim Pause, PhD, and Stephen Lee, PhD, studiedthe effect of growth factor withdrawal on kidney cells that were positiveor negative for production of the protein produced by the VHL gene (pVHL).

They found that the cells that produced pVHL exited the cell cycle andentered the quiescent G0 phase after growth factor withdrawal. In contrast,the pVHL-negative kidney cancer cells failed to leave the cell cycle, insteadcontinuing through several replication cycles, a process thought to initiatetumor formation. "These observations suggest that pVHL is regulatingthe ability of cells to enter quiescence in response to growth factor withdrawal,and might explain why the VHL gene has a gatekeeper function in the kidney,"Dr. Pause said. "The VHL protein might be part of a pathway that isdisrupted in many types of cancer."

The research is especially exciting, Dr. Friend said, as it relatesto cytotoxic cancer treatments. "If you were to ask how many physiciansin the audience had ever seen a case of von Hippel-Lindau disease, it'sprobably one in a hundred or less," Dr. Friend said, "and yetby studying this rare genetic disease, the NCI researchers came upon aclue that may be pivotal to understanding why cancer therapies don't workbetter than they do."

When treating cancer, he noted, "we want all of the cells to becycling because in that instance, we can actually treat all of them. It'sthe quiescent ones that don't give themselves up to be killed that stayaround and cause trouble."

Rather than labeling the research a major cancer breakthrough, Dr. Friendcalled it "the type of clue that in the past has led to breakthroughs."

He suggested that many scientists were inspired by the von Hippel-Lindaugene presentation. "I think everyone left the meeting thinking, Whatexperiments can I do that might take advantage of this new knowledge."