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.