If you’re like most Americans, either you or someone you know has probably been affected by cancer. And close to another million and a half more people will hear from their doctors for the first time this year that they have some form of the disease.
I was thinking about those people as I sat in on sessions at the annual meeting of the American Society of Clinical Oncology in Atlanta, where cancer researchers and doctors from all over the world come to report on their latest studies. It has been five years since the drug Gleevec, introduced at this conference, electrified doctors, grabbed headlines and changed the way doctors think about treating cancer. Because Gleevec was exquisitely targeted to interrupt a specific step in the cancer cell’s growth process, it heralded a new era of kinder, gentler treatments that would pack all the anti-cancer wallop of chemotherapy without the toxic side effects.
But five years later, while these so-called targeted drugs have certainly changed cancer treatment, they have not had quite the impact that all the fanfare promised. People are still getting cancer, and still dying at almost the same rate as they were when surgery and chemotherapy were their only options. So what happened?
It turns out that Gleevec was a Cinderella story — a perfect matching of drug to cancer. The specific cancers for which Gleevec has wrought such miracles — chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST) — rely pretty exclusively on a pathway that Gleevec targets, making these diseases ideal victims for a targeted therapy. But breast, lung, colon and prostate cancers, the leading types of cancer in the U.S., aren’t as accommodating.
So that’s why doctors at ASCO were taking the next logical step: if one drug isn’t enough to control these tumors, then maybe creating a cocktail of several drugs, and adding them to chemotherapy, will be. In some ways, it’s a fallback strategy, says Dr. Leonard Saltz, a colon cancer specialist at Memorial Sloan-Kettering Cancer Center. “Nobody set out to develop [these drugs] as an additive to chemotherapy,” he says. “They were supposed to replace chemo, and make us look back and say, Can you believe that we had a barbaric age when we were treating patients with something that made them lose their hair and vomit their guts out?’ But they didn’t work, and if you can’t beat them, join them.”
So doctors may have to become molecular chefs, cooking up new anti-cancer recipes with a growing number of promising drug ingredients. If the number of presentations at ASCO is any indication, their lab cupboards are plenty full of just such compounds. So far, the best cocktails, still in early testing in the most advanced cancer patients, try to include some agents aimed at cutting off a tumor’s blood supply (so-called angiogenesis inhibitors), others designed to trigger a cancer cell’s pre-programmed suicide pathway, or still other compounds that muck up the intricate signaling system that a cancer cell uses to guide and control its growth. Scientists are also turning their attention to metastasis, which is responsible for over 90% of the deaths from solid tumor cancers, by finding the genes and pathways responsible for launching tumor cells to distant sites. By blocking these pathways, they hope to keep cancer corralled and prevent it from spreading to other parts of the body, where it becomes more difficult to treat.
All this sounds incredibly logical, but it has also led researchers to talk about their results earlier and earlier. It used to be that only wild horses would get a scientist to report on Phase I of a drug trial — the first study of a drug in human patients, which usually involve a handful of the sickest patients who have not responded to standard treatments. The purpose of Phase I studies is to establish what’s known as the maximum tolerated dose — that is, the dose at which the drug then becomes too toxic and dangerous to take. But because the number of patients is too small and the safety of the drug hasn’t been established, such tests are not designed to determine the drug’s effectiveness.
But at ASCO this year, a stunning number of Phase I studies were front and center, in key sessions attended by thousands of doctors. As I heard scientist after scientist report on his Phase I work, sometimes involving as few as a dozen patients, I wondered whether these early presentations had anything to do with the promise of the targeted therapies.
So I asked Dr. Branimir Sikic, a professor at Stanford University School of Medicine who chaired the committee that designed ASCO’s program. “It’s correct that there were more Phase I studies in the clinical science symposia,” he told me. “And we did that deliberately. It was a way to inform both practicing [cancer doctors] and clinical researchers about early data and the scientific background of new targets. We now have a huge amount of scientific research and much more knowledge in depth of why we should be targeting a particular gene or protein and how these drugs might work.”
All this is good news for patients, as long as they remember that, as promising as drugs sound in Phase I, they still have a long way to go before they make it to the pharmacy, if they make it at all. But with more candidates in the cancer kitchen, better cocktails are bound to emerge. “For those of us in cancer research, it’s a very exciting time,” says Sikic. “And we’re hoping that with every year, it’s going to be a better and better time to be a cancer patient.”
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