Cancer: A Huge Leap Forward

An underreported revolution in cancer treatment is giving hope to people who have this illness now—or fear they’ll get it in the future

by Katharine Davis Fishman
Photograph: Illustration by Mark Allen Miller

Genetically targeted drugs aim to disrupt the growth and spread of cancer cells. Normally, your body’s cells divide in a controlled manner, but with cancer, some cells go crazy and clone themselves rapidly. Often the clones form tumors, and those tumors, if not removed in time, may send out colonies of cloned cells that multiply relentlessly in other parts of the body. Think of what happens when a virus corrupts your computer.

Each cancerous cell’s behavior is governed by instructions it receives from a protein, which in turn takes its orders from a mutated gene. One simple example of a cancer-causing mutation happens when the ends of chromosomes 22 and 9 break off and trade places. The product of this bizarre translocation, known as the Philadelphia chromosome, creates a protein that signals white blood cells to reproduce unchecked, causing a disease called chronic myelogenous leukemia (CML).

Gleevec is a drug designed to inhibit this mutation, which is found in all CML patients. In the drug’s first clinical trial, 53 out of 54 patients experienced complete remission, making Gleevec arguably the most successful targeted medication in existence. It is also one of the earliest: Gleevec came on the market in 2001. Nearly two thirds of the clinical trial’s original patients stayed on it. About 17 percent developed resistance within five years, and many were shifted to a -second-generation drug, on which they are still being maintained.

One reason Gleevec is so successful is that it targets “the best and most well-defined molecular abnormality known in oncology,” according to its developer, Brian Druker, MD, of Oregon Health and Science University. Most other cancers result from several constantly changing mutations, which makes them much more difficult to treat. So the future of cancer therapy lies in cocktails of different drugs, which may combine a targeted drug with either a traditional chemotherapy or another type of cutting-edge approach, or both. The goal is to turn cancer into a chronic disease like AIDS, giving patients a more or less normal life span, provided they continue to take the appropriate drugs.

The new normal versus the old normal

Kari Worth of Napa, California, now 46, had staved off stage 4 melanoma for six years, but in 2009 the cancer recurred. By that time, two miracle drugs had been introduced. The first was ipilimumab, a form of immunotherapy that harnesses the patient’s immune system to attack the disease. The second was vemurafenib, a targeted drug aimed at the BRAFmutation in skin cells that’s evident in half the patients with melanoma.

“The great majority of patients who have the BRAF mutation respond to the targeted drug vemurafenib within a few weeks,” says University of California, Los Angeles, oncologist Antoni Ribas. Early tests of vemurafenib produced astonishing results: Melanoma tumors shrank and even vanished; patients got out of their wheelchairs and walked again. But after six or seven months, on average, the tumors began to reappear, for different reasons. Sometimes tumors developed new mutations or other alterations; other times the cancer cells found ways to evade the drug. In short, says Ribas, vemurafenib works for a lot of patients, but its benefits are often “not durable.”

In contrast, he notes, “the immunity drug ipilimumab gives a benefit to just a small proportion of melanoma patients, but that improvement tends to be lasting.” So oncologists have been testing a combination of these two drugs, both of which are approved by the FDA and are on the market. “We’re developing a whole bunch of clinical trials that try to improve both agents,” says Ribas. New trials either combine vemurafenib with the immunotherapy drug or pair it with a newer drug that targets another mutation, potentially thwarting the development of resistance and also decreasing side effects.

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01.30.2013

In my opinion, this story is particularly informative and well-written.

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