Why One Dumb Tumor Is Smarter Than 100 Oncologists
This week’s story paints a fairly bleak picture of cancer therapy 37 years after the start of the war on cancer, but as I spoke to some of the nation’s leading oncologists about their memories of when they first entered the field, I was struck by two things: the real progress that has been made since 1971, and their remarkable ability to remain hopeful in the face of a disease that, 1,500 times a day (that's how many people in the U.S. will die of cancer every day this year), reminds them that cancer keeps winning far too many battles.
David Johnson of Vanderbilt-Ingram Cancer Center was in medical school in 1971, the year Richard Nixon declared war on cancer in his State of the Union speech. Oncology wasn’t even recognized as a medical specialty, Johnson recalled to me. “Cancer wasn’t something you talked about much, except to note that it existed and that patients didn’t do well,” he said.
The first cancer patient Johnson had as a young resident was a man with small-cell lung cancer. “It was so rapidly progressive,” he said. “Patients might live a few weeks without treatment. I remember preparing for my presentation to the attending physician, spending hours in the library to learn everything I could about this disease. As we moved down the hallway to this patient’s room, I became increasingly anxious. I’ll never forget it as long as I live: I began, saying 'Mr. So-and-so is a 63-year old man with a diagnosis of small-cell lung cancer . . . ' And the attending shook his hand in my face: ‘this is not a disease for which we have a lot to offer; let’s move on.’”
Johnson’s initial reaction, he recalled to me, was that he was off the hook as far as presenting the case went. But then he felt mounting frustration. “I said to myself, wait a minute, why isn’t there something we can do for this man?” Johnson told me. “It influenced my thinking about cancer from then on. The whole idea of going to medical school was to help people. If doctors can’t do anything, there’s something wrong with this picture.”
By the mid-1970s, oncologists had made some progress against the liquid cancers, as they’re called—leukemias and lymphomas—and had shown that giving chemotherapy after a women with breast cancer has had a mastectomy increases the chance that she’ll remain cancer-free and survive. “For solid tumors, there was a presumption that the cytotoxic drugs used in leukemia would also work,” Johnson recalled, “but these cancers didn’t respond as well. The reason leukemias are vulnerable [to chemo agents that barely lay a glove on solid tumors] is that the disruption in the signaling pathways aren’t as complex as they are in solid tumors: there are maybe one or two in leukemias compared to 20 or 40 in solid tumors.”
That was the most common refrain I heard as I spoke to one after another oncologist about why, as one put it to me, the dumbest cancer is smarter than the most brilliant oncologist: cancer cells can use any of dozens if not scores of biochemical pathways to proliferate and spread. Stop one and the cells turn on a different one, kind of like squeezing a balloon squashes it here but just makes it bulge out somewhere else.
Johnson specializes in lung cancer, as did a few oncologists I spoke to, and every one of them was remarkable for his or her unflagging optimism against an implacable foe (lung cancer is the nation’s leading cancer killer). In Johnson’s case, he remembers vividly the first baby steps toward fighting this disease, in the mid-1970s and early 1980s,when some of the DNA-breaking drugs such as methotrexate shrank tumors. But as would become clear even with the much-ballyhooed targeted therapies, shrinking a tumor does not mean cure or even, necessarily, long-term remission.
“The more recalcitrant tumors have redundant systems to let them escape from what we throw at them,” Johnson told me. “In lung cancer, each cell has multiple abnormalities, and one cell might be next to one with eight different abnormalities. These solid tumors have the capacity to elude the various therapies we throw at them. A solid tumor goes away on an x-ray, and then it comes back: you’d have to be a functional moron not to realize that the cancer cell has figured out how to get around the therapy.”
The goal is to keep throwing different therapies at the cancer, choosing the therapies so that they target the precise proliferation pathways the cancer is using. “We are truly within a few years of being able to profile tumors so that I can say to a patient, ‘we shouldn’t use this drug on you, because it won’t help, but we should use this one,’” Johnson said.
When I asked Johnson how he felt about critics who say we have made embarrassingly little headway against cancer since 1971, he said, “I don’t know any investigator or clinician who’s satisfied with the progress that’s been made.”
The fact that cancers elude chemotherapy so often raises the obvious question: how does anyone go into remission and stay there, truly beating cancer? Some ideas on that tomorrow.