Closing in on a Cure
Pink reigns in October, the month to raise national awareness of the 274,900 women who will be diagnosed this year with breast cancer and the 41,000 who will die of advanced disease. Most women fear that this cancer might well be theirs or their daughters' someday and are now passionate about the importance of mammograms to find early disease when it's most curable. But the legacy of pink activism is much greater than its success with early detection. The 20-year burst of intense research it has inspired, coming fortuitously just as the genomics revolution was taking off, is now producing huge payoffs. In the past month alone, there have been advances on two fronts: A powerful new drug for women with the worst form of breast cancer is in the government approval pipeline, and scientists have uncovered new clues to the mechanism behind metastatic breast cancer's spread.
GlaxoSmithKline's new drug, Tykerb (lapatinib), is designed to foil the cancer gene HER2/neu, which codes for a protein that drives breast tumors to be especially aggressive and is present in 30 percent of women with breast cancer. Genentech's groundbreaking drug, intravenously administered Herceptin (trastuzumab), goes after this gene by lathering the outside of the cancer cell with antibodies to neutralize the HER2 protein. This slows or stops the growth of metastatic tumors and cuts in half the expected recurrence among women with less advanced disease.
Tykerb counters the same HER2/neu gene, plus a second gene, in a different way: A small molecule, it slips inside the cancer cell and throws a monkey wrench into the genes' internal signaling networks. Tykerb's molecules are small enough to penetrate the brain; early studies show patients experience fewer and smaller brain metastases. The drug sounds too good to be true: It causes only minor side effects, comes in pill form so it can be taken at home, and, when added to standard therapy, offers even the sickest patients an average of four extra months of life free from cancer progression.
The holy grail, of course, would be to make breast cancer progression obsolete, to turn those four months into 40 and, in time, a natural life span. But this will happen only if we can solve the mystery of what makes a localized cancer morph into a widely disseminated disease. The recent work of several groups of scientists has brought us closer to that goal.
In 2003, researchers at the University of Michigan Comprehensive Cancer Center realized that a small number of cancerous cells scattered through breast cancer tissue had all the properties of stem cells. Typically, we think of stem cells as forces for good, which use their primitive powers of perpetual self-renewal and the ability to travel freely to help repair or replace injured cells. But breast cancer stem cells are no-goods, roaming through the body only to spread new tumors. Earlier this month, researchers from the Keck School of Medicine at the University of Southern California reported in the journal Clinical Cancer Research that fully 71 percent of the tumor cells they examined in the earliest of breast cancer metastases had stem cell-like traits-strongly suggesting that they, as the accompanying editorial puts it, are "lethal seeds" of tumor dissemination.
Dual attack. These discoveries point to an entirely new way to think about cancer and how to beat it: Home in on the rapidly growing mass of tumor cells, as drugs like Herceptin and Tykerb do, and target tumor-initiating stem cells at the same time. Too often now, treatment may look like a grand success when it shrinks or eliminates visible tumors, even as their dormant seeds lie in wait until the environment is right to sprout again.
With current technology, scientists can sift out from a tumor mass the hardy stem cells and study their genes with the aim of designing an entirely new class of targeted drugs-just as study of the oncogene HER2/neu led to Herceptin and Tykerb. If they succeed, oncologists would offer patients with advanced and metastatic cancer-who are so often given up as lost-a chemo cocktail containing drugs that stop the visible mass of tumor cells in its tracks and at the same time kill off the cancer's lethal seeds. Metastatic breast cancer would be controlled, if not cured.
Malignant stem cells have now been identified in numerous other cancers, triggering new thinking about them as well. For all of us, the women in pink are leading the way once again.
This story appears in the October 23, 2006 print edition of U.S. News & World Report.
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