MEDICINE Cancer therapies fall short of what researchers hoped

Some researchers say cancer will never be cured but perhaps it can be controlled.
ASSOCIATED PRESS
Not long ago, the defeat of cancer seemed inevitable. Decades of research would soon pay off with a completely fresh approach, an arsenal of clever new drugs to attack the very forces that make tumors grow and spread and kill.
No more chemotherapy, the thinking went. No more horrid side effects. Just brilliantly designed drugs that stop cancer while leaving everything else untouched.
Those elegant drugs are now here. But so is cancer.
A tough time
The approach, which appeared so straightforward, has proved disappointingly difficult to turn into broadly useful treatments. Some now wonder if malignancy will ever be reliably and predictably cured.
The dearth of substantial impact so far suggests the fight against cancer will continue to be a tedious slog, and victories will be scored in weeks or months of extra life, not years. The full potential of the new approach may take decades to be realized.
The drugs, called targeted therapies, are intended to arrest cancer by disrupting the internal signals that fuel its unruly growth. Unlike chemo, which attacks all dividing cells, these medicines are crafted with pinpoint accuracy to go after the genetically controlled irregularities that make cancer unique.
Several have made it through testing, but despite their apparent bull's-eye hits, lasting results are rare. Instead, these new drugs turn out to be about as effective -- or as powerless -- as old-line chemotherapy. Aimed at the major forms of cancer, they work spectacularly for a lucky few and modestly for some.
But for most? Not at all.
What's wrong?
Doctors have many theories about what's gone wrong. But it is clear that cancer is a surprisingly robust foe, packed with convoluted backup systems that kick in when threatened by the new drugs.
At best, experts now expect knocking down cancer will require an elaborate mixture of targeted drugs, assembled to match the distinct biology of each person's cancer.
"It's a much more complicated problem than anyone ever appreciated," says Dr. Leonard Saltz, a colon cancer expert at Memorial Sloan-Kettering Cancer Center. "It will, unfortunately, be with us for a long time."
The job is so daunting, especially for advanced cancers propelled by potentially dozens of nefarious genetic mutations, that scientists are even rethinking the goal of cancer research.
"Society as a whole, and most of the medical profession, have it wrong understanding we'll wake up one morning and find out cancer is cured. It won't happen. The public should give it up," says Dr. Craig Henderson, a breast cancer specialist at the University of California, San Francisco, and president of Access Oncology, a drug developer.
"What we have learned by these billions of dollars invested in cancer biology is that cancer are us," he goes on. True, cancer is different. But not different enough. "Identify what makes cancer unique and wipe it out? That won't happen. We cannot wipe out the cancer without wiping out a lot of the rest of us."
Shifted sights
Henderson and many others have shifted their sights to something less -- converting cancer into a chronic disease, like diabetes or AIDS. Treatments might slow or even stop its worst effects so people survive for years reasonably free of symptoms.
Dr. Andrew von Eschenbach, head of the National Cancer Institute, argues that a cure is not even necessary if this can be done, something he optimistically hopes to see by 2015. But eliminate cancer? "Not in the foreseeable future," he says.
Still, experts concede there is no firm evidence that targeted treatments will tame cancer to a chronic condition, either. Certainly, the ones tested so far do not often come close to this for the common varieties, such as lung, breast, colon and prostate cancer.
The drug that initially raised hopes in the 1980s, Herceptin, became a standard treatment for spreading breast cancer, typically delaying progression by a few months in the quarter of victims with a particular genetic profile.
Since Herceptin, targeted drugs have become the prevailing approach in cancer research. Whenever any of these make slight progress, the news is widely and sometimes breathlessly reported. An estimated two-thirds of the nearly 400 cancer medicines in human study take this tack. Yet researchers do not envision successes any more spectacular from this pipeline than the modest effects of the handful already on the market.
Ultimate outcome
"Right now, in the short run, we can bring an occasional miracle and have an overall small benefit," says Dr. John Glaspy, medical director of UCLA's surgical oncology center. "But there has not been a major improvement on what happens to them ultimately."
Furthermore, the dream of abandoning chemotherapy has largely evaporated. Even the targeted drugs' small benefits are typically seen only when combined with standard chemo.
Cancer doctors facing waiting rooms full of dying cancer patients, with little to offer but easing misery and perhaps a few extra months of survival, clearly had wished for more.
"The hope was that these targeted therapies would be the new magic bullet and would cure cancer," says Dr. David Decker, an oncologist at William Beaumont Hospital outside Detroit. "It's fair to say they haven't panned out the way we thought they would."