In 2003, when Kari Worth was diagnosed with stage 4 melanoma, treatments were limited, so she underwent what’s called biochemotherapy, a taxing regimen that repeatedly delivers an infusion of three chemo drugs and two immunotherapy drugs, producing devastating side effects such as extreme nausea and systemic inflammation. “It was horrendous,” she recalls. “I was hospitalized 25 times in two and a half years.” But the treatment worked. Once Worth had surgery to remove a tumor from her lung, where the cancer had spread, she was pronounced NED, “no evidence of disease.”
By the time Worth was back fighting cancer in 2009, her treatment was nothing like what she had previously endured. At UCLA she was given the targeted drug vemurafenib, which she took twice a day at home. “Initially my tumor went away and everything was good, but 10 months later the cancer came back,” she says. After surgery that removed a pectoral muscle, Worth was briefly stable and then began the immunity drug ipilimumab, which bought her three months until the melanoma reached her brain and was treated with Gamma Knife radio-surgery, a precisely targeted, noninvasive radiation procedure. This was followed by more ipilimumab, which appeared to halt the cancer. As of fall 2012, Worth had been through 12 infusions of ipilimumab and more radiation and was in a two-year trial of a promising new immunotherapy drug called Merck MK 3475, which involves 30-minute infusions every three weeks and produces minimal side effects.
At the same time Worth’s life has been saved, it has also been changed. “I used to have a career, but being treated for cancer is pretty much a full-time job,” she says. “I have an 11-year-old and a 12-year-old. My kids don’t treat me any differently. I’m just their mom, and I do the laundry and everything else. I’m busy, and life is full.”
Even with the new drugs, a true cure—defined as permanent remission—may not always be possible. “I tell people that dealing with cancer is a marathon, not a sprint,” says Lecia Sequist, MD, an oncologist specializing in lung cancer at Mass General. “What we’re trying to do is get six months out of this treatment and three months out of the next treatment, then four months out of the next. We’re trying to piece together a series of treatments, and every year theories advance. If we can just get you to next year, then our goal will be to get you to the year after.”
An explosion of information
Achieving that goal has become more and more likely: The pace of finding new genetic targets is really speeding up, in part because of the work of The Cancer Genome Atlas (TCGA), funded by the National Institutes of Health. For instance, last September a team of TCGA researchers led by the pathologist and cancer researcher Matthew Meyerson, MD, PhD, of the Dana-Farber Cancer Institute in Boston published the first comprehensive genome analysis of squamous cell lung cancer, a major and hard-to-treat type that causes 40,000 deaths a year and for which no targeted therapies exist. Analyzing 178 tumors, the researchers discovered multiple genes with significant mutations that might be targeted by drugs currently in clinical trials (some for other diseases) and that could be tried on patients with this particular form of lung cancer.
The study is just one of 20 genetic analyses of different types of cancer that TCGA is scheduled to complete by 2014. Focusing on cancers with a poor prognosis and a large public health impact, TCGA gathers and evaluates cancerous tissue samples from research institutions across the country and releases the results in a public database. Meyerson credits the fast discovery of additional molecular targets to a spectacular fivefold-to-tenfold improvement in genome-sequencing technology over the past few years, to which TCGA is contributing. “It’s amazing to think what we’re doing today compared to five years ago. The quantity is better, the quality is better,” he says.