BY HER SIDE. Bernadine Healy and her husband, Fred Loop, M.D., former head of the Cleveland Clinic, at their home.
This is not the case for most patients who face invasive cancer. Cancer treatment has a risk-benefit analysis all its own; the therapy is rough and toxic to an extent that seems almost to challenge the medical precept "First, do no harm." If this is going to change, it will be for one major reason: Because cancer is a disease of genes and their proteins, we must understand their networks and interactions.
Fortunately, the revolution is already underway. The Human Genome Project was a boon for accelerating our knowledge about genes, the masters of cancer's fate. As a follow-up, the Cancer Genome Atlas will put the focus on cancer treatment, sketching out blueprints for the dysfunctional molecular networks that turn a cell cancerous. And sifting through the genetic and molecular profiles of individual cancers has exposed a big secret that misled many treatments of the past: What seem to be identical tumors under the microscope can be markedly different where it really matters, in the genes and proteins. This is a crucial discovery, explaining for the first time why a tumor melts away under a particular therapy while another of the same type is barely touched, why one tumor returns in a few years yet another disappears for a lifetime. And it is a discovery that demands a rethinking of the traditional treatment approach, in which any and all cells with rapidly replicating DNA—malignant or not—are attacked as if they were known enemies of the body. The new era instead relies upon an armory of laserlike drugs, some old, some new, some yet to be devised, that specifically target deranged genetic pathways and swoop in for the kill, leaving the innocent bystanders intact.
There's another, even subtler goal. If we can read the signs of future malignancy early enough, it should be possible to intervene in the life of misbehaving cells, reforming and redirecting them before they commit to the dark side. To be sure, we are in the early phase of this new model. In my own predicament, I was lucky to find myself, in a small way, on the initial crest.
The standard treatment for most brain tumors is surgery followed by radiation. In the past, chemotherapy has been considered a bust because of a natural protective wall, called the blood-brain barrier. Specialized cells that line the brain's blood vessels create tight junctions impermeable to all but the brain's essential shopping list of small molecules such as glucose and oxygen. This barrier, so important to isolating the brain from blood-borne disease, also shields brain malignancies from many commonly used chemotherapy drugs that might otherwise destroy them. Historically, chemotherapy for brain tumors was the "salvage therapy" when all other options had been exhausted. And sometimes, mysteriously, a tumor did respond.
I told my medical team that radiotherapy was not for me. Though this treatment typically makes brain tumors shrink and can lengthen life, long-term exposure to the radiation also puts patients at risk for memory and cognitive difficulties. That was one risk I chose not to take, a conviction formed more by the patient in me than from any bias I had as a physician. I wanted nothing more than just to be me for as long as possible—with my kids, with my husband, at home, at work. Plus as a lifelong geek, I could not bear to threaten this brain of mine that had done me so well over the years.
Unknowns. The decision was not made without a lot of thought. Each doctor on the brain tumor team—which I dubbed my "brain trust"—brought his own perspective. We all knew of studies showing that at least some patients with my tumor seemed to do well with chemo alone. But that was nonetheless not accepted therapy, as the clinic's radiation oncologist stressed to us.
Barnett acknowledged how little we knew about the unusual properties of my tumor. From his perspective, there was no real evidence to guide us to a certain path, and good old-fashioned clinical judgment and patient choice had to weigh in heavily. The neuro-oncologist who would be providing the treatment, David Peereboom, was comfortable delaying radiation if the tumor proved sensitive to drugs.
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