More puzzled by her symptoms than alarmed — this nausea came without any aura of pain — she saw her internist. She was given a diagnosis of gastroenteritis and sent home to bed rest and Gatorade.
But the nausea persisted, and then additional symptoms appeared out of nowhere. Ghostly fevers came and went. She felt perpetually full, as if she had just finished a large meal. Three weeks later, she returned to the hospital, demanding additional tests. This time, a CT scan revealed a nine-centimeter solid mass pushing into her stomach. Once biopsied, the mass was revealed to be a tumor, with oblong, spindle-shaped cells dividing rapidly. It was characterized as a rare kind of cancer called a gastrointestinal stromal tumor, or GIST.
A surgical cure was impossible: her tumor had metastasized to her liver, lymph nodes and spleen. Her doctors halfheartedly tried some chemotherapy, but nothing worked. "I signed my letters, paid my bills and made my will," the patient recalled. "I was told to go home to die."
In June, several months after her diagnosis, she stumbled into a virtual community of co-sufferers — GIST patients who spoke to one another online through a Listserv. In 2001, word of a novel drug called Gleevec began to spread like wildfire through this community. Gleevec was the exemplar of a brand-new kind of cancer medicine. Cancer cells are often driven to divide because of mutations that activate genes crucial to cell division; Gleevec directly inactivated the mutated gene driving the growth of her sarcoma, and in early trials was turning out to be astonishingly effective against GIST.
The psychologist pulled strings to enroll in one of these trials. She was, by nature, effortlessly persuasive, and her illness had made her bold. She enrolled in a Gleevec trial at a teaching hospital. A month later, her tumors began to recede at an astonishing rate. Her energy reappeared; her nausea vanished. She was resurrected from the dead.
Her recovery was a medical miracle, emblematic of a new direction in cancer treatment. Medicine seemed to be catching up on cancer. Even if no cure was in sight, there would be a new generation of drugs to control cancer, and another when the first failed. Then, just short of the third anniversary of her unexpected recovery, cancer cells suddenly began multiplying again. The dormant lumps sprouted back. The nausea returned. Malignant fluid poured into the cisterns of her abdomen.
Resourceful as always, she turned once more to the online community of GIST patients. She discovered that there were other drugs — second-generation analogues of Gleevec — in trial in other cities. Later that year, she enrolled in one such trial in Boston, where I was completing my clinical training in cancer medicine.
The response was again striking. The masses in her liver and stomach shrank almost immediately. Her energy flowed back. Resurrected again, she made plans to return home. But the new drug did not work for long: within months she relapsed again. By early winter, her cancer was out of control, growing so fast that she could record its weight, in pounds, as she stood on the hospital's scales. Eventually her pain reached a point when it was impossible for her to walk.
Toward the end of 2003, I met her in her hospital room to try to reconcile her to her medical condition. As usual, she was ahead of me. When I started to talk about next steps, she waved her hand and cut me off. Her goals were now simple, she told me. No more trials. No more drugs. She realized that her reprieve had finally come to an end. She wanted to go home, to die the death that she expected in 1999.
The word "relapse" comes from the Latin for "slipping backward," or "slipping again." It signals not just a fall but another fall, a recurrent sin, a catastrophe that happens again. It carries a particularly chilling resonance in cancer — for it signals the reappearance of a disease that had once disappeared. When cancer recurs, it often does so in treatment-resistant or widely spread form. For many patients, it is relapse that presages the failure of all treatment. You may fear cancer, but what cancer patients fear is relapse.
Why does cancer relapse? From one perspective, the answer has to do as much with language, or psychology, as with biology. Diabetes and heart failure, both chronic illnesses whose acuity can also wax and wane, are rarely described in terms of "relapse." Yet when a cancer disappears on a CT scan or becomes otherwise undetectable, we genuinely begin to believe that the disappearance is real, or even permanent, even though statistical reasoning might suggest the opposite. A resurrection implies a previous burial. Cancer's "relapse" thus implies a belief that the disease was once truly dead.
But what if my patient's cancer had never actually died, despite its invisibility on all scans and tests? CT scans, after all, lack the resolution to detect a single remnant cell. Blood tests for cancer also have a resolution limit: they detect cancer only when millions of tumor cells are present in the body. What if her cancer had persisted in a dormant state during her remissions — effectively frozen but ready to germinate? Could her case history be viewed through an inverted lens: not as a series of remissions punctuated by the occasional relapse, but rather a prolonged relapse, relieved by an occasional remission?
In fact, this view of cancer — as tenaciously persistent and able to regenerate after apparently disappearing — has come to occupy the very center of cancer biology. Intriguingly, for some cancers, this regenerative power appears to be driven by a specific cell type lurking within the cancer that is capable of dormancy, growth and infinite regeneration — a cancer "stem cell."
If such a phoenixlike cell truly exists within cancer, the implication for cancer therapy will be enormous: this cell might be the ultimate determinant of relapse. For decades, scientists have wondered if the efforts to treat certain cancers have stalled because we haven't yet found the right kind of drug. But the notion that cancers contain stem cells might radically redirect our efforts to develop anticancer drugs. Is it possible that the quest to treat cancer has also stalled because we haven't even found the right kind of cell?
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http://www.nytimes.com/2010/10/31/magazine/31Cancer-t.html?ref=magazine&src=me&pagewanted=print
