Cancer: A Long List of Missed Opportunities

Mea culpa: Lab Notes was missing in action last week because I couldn’t tear myself away from interviewing oncologists for the story in this week’s magazine [] about the war on cancer. I wanted to chart the progress that has been made against the disease in the 37 years since Richard Nixon launched the war on cancer, and that meant talking to researchers and clinicians who have been in trenches for several decades. 

Their stories were heartbreaking, not only for the patients they lose but for the missed opportunities.

Gerold Bepler, chief of the division of thoracic oncology (that’s lung cancer) at H. Lee Moffitt Cancer Center, started his Ph.D. thesis on Hodgkin’s lymphoma in 1980 and then turned to lung cancer as a post-doctoral fellow. He recalled that the big breakthroughs in lung-cancer chemotherapy 25 years ago let patients with small-cell lung cancer survive a year instead of six-to-eight weeks, as had been the case before cisplatinin and other drugs were developed. “With non-small-cell lung cancer,” he recalls, “the response rate was much lower, maybe 15 to 20 percent, and it had remarkable toxicity. You wondered, were you really helping people if you made them so sick for the little extra time that you kept them alive?”

“The next breakthroughs were anti-nausea drugs in the mid-1980s to early 1990s. Cisplatinin became much easier to give. I remember people throwing up for a week at a time, before these drugs, when they got chemo once every three weeks. Suddenly, with the anti-nausea drugs, chemo became tolerable,” Bepler told me.

And what counts as progress against lung cancer? In the 1990s, 14 to 15 percent of patients lived at least five years. Today, Bepler said, 16 to 17 percent do. “It’s a very small number, and we are far, far, far from being able to cure this disease.”

Why is it so tough to treat? “Lung cells have developed mechanisms to cope with genotoxic stress,” Bepler told me. That means that the chemo drugs that act by damaging DNA, so that malignant cells cannot replicate, eventually stop working: the cancer cells turn on DNA-repair mechanisms or other pathways that render the chemo agents useless.

Like so many of the scientists I interviewed, Bepler points to many missed opportunities over the 37 years of the war on cancer. In his case, he proposed a study in the mid-1990s in which researchers would have taken samples of lung cancers, analyzed and stored them, and then determined which molecular profiles predicted response to which existing or future chemo drugs. “I struggled to get NCI [National Cancer Institute] approval,” Bepler said. “What gets funded depends on what people think at the time is hot, or in. I’ve served on NCI study sections [those are the panels of, usually, outside scientists who review grant proposals and score them, determining which get funded] so I can see it from both perspectives. When you start reading the applications, you are automatically drawn to the ones perceived to be interesting,” sometimes losing sight of the fact that the goal here is to treat cancer and not (only) discover cool things about the molecular biology of cancer. “In my case, people thought the idea couldn’t be implemented in patients because they didn’t think patients would be willing to have repeated biopsies,” which is what would have been required to match their tumor to a particular chemo drugs.

Yet that is what the current era of personalized cancer therapy is about. Bepler isn’t the only researcher who wanted to go down that path more than a decade ago. If he and others had been funded, who knows how much further we would be in the fight against lung cancer?
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