- The Washington Times - Monday, July 28, 2003


Not long ago, the defeat of cancer seemed inevitable. The thinking was that decades of research would soon pay off with a completely fresh approach: an arsenal of clever new drugs to attack the forces that make tumors grow and spread and kill.

No more chemotherapy, the understanding 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.

The approach, which appeared so straightforward, has proven disappointingly difficult to turn into broadly useful treatments. Some wonder whether malignancy will ever be reliably and predictably cured.

The dearth of substantial effect suggests that the fight against cancer will continue to be tedious and hard, 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.

At best, experts now expect that 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,” said Dr. Leonard Saltz, a colon cancer expert at the 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 potentially by 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 a wrong understanding we’ll wake up one morning and find out cancer is cured. It won’t happen. The public should give it up,” said Dr. Craig Henderson, a breast cancer specialist at the University of California at San Francisco and president of Access Oncology, a drug developer.

Dr. Henderson and many others have shifted their sights to something less — converting cancer into a chronic disease, such as diabetes or AIDS. Treatments might slow or even stop the disease’s worst effects so that people survive for years reasonably free of symptoms.

Still, experts concede, there is no firm evidence that targeted treatments will tame cancer to a chronic condition, either. Certainly, the ones tested do not often come close to this for the common varieties, such as lung, breast, colon and prostate cancers.

Although targeted therapies have origins in basic cancer discoveries of the 1980s, the story for many began at a meeting of the American Society of Clinical Oncology in 1998. Researchers were thrilled to hear of the first convincing demonstration that a targeted drug could slow the course of cancer even a little. It was proof that the principle is sound.

Usually wary oncologists rhapsodized about a new era of treatment. “A tidal wave,” one of them called it. Even then, no one predicted quick cures. But they clearly felt they at least had the key to getting inside cancer and fixing it.

The targeted drugs have been most impressive against cancers of the blood and immune system, which are easier to control than the more common organ tumors.

Though they had hoped for more, many cancer specialists seem relieved to have anything new to offer at all. Even small advances are welcome in a profession in which progress often seems glacial.

“It is slower progress than we’d like, but that’s the nature of medicine,” said Dr. Donald Trump, chairman of medicine at Roswell Park Cancer Institute in Buffalo, N.Y. “A disease process as complex as cancer is unlikely to yield to blockbuster effects.”

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