With all the ways cancer cells can elude chemotherapies (as well as radiation, for some of the same reasons: radiation damages DNA, but malignant cells activate DNA-repair mechanisms), it may seem a miracle that anyone beats cancer. Yet clearly, millions of people do; some living with it for decades, others having no detectable malignancies by the end of treatment. What gives?

I put this question to Keith Block, an innovative oncologist who runs the Block Center for Integrative Cancer Treatment in Evanston, Illinois, and who is also the director of Integrative Medical Education at the University of Illinois College of Medicine, editor-in-chief of the journal Integrative Cancer Therapies, and scientific director of the Institute for Integrative Cancer Research & Education. As you can tell from the names of the programs Block is involved in, he practices integrative care: he uses all of the standard chemo and radiation treatments, but supplements those with a program of fitness, diet and mind-spirit interventions (stress reduction, improving sleep and the like).

The goal of the latter is not only to make getting through treatment less torturous (Block's diet and natural supplement programs include steps to reduce nausea, for instance), but also—primarily, I should say—to improve patients’ chance of surviving. Many, many patients with cancer actually die not from failure of an organ that cancer has attacked, but from things such as embolisms (clots in the lung, often thrown off by a tumor), pneumonia (from a weakened immune system), sepsis and wasting—in short, secondary consequences of the cancer. Patients with, say, lung cancer who die of an embolism are usually categorized as dying of their cancer—that’s how the hospital classified them when they entered, and that’s how it classifies them when they leave—so these causes of death don’t show up in cancer mortality data. But Block believes that targeting them could significantly extend survival, and in patients who do make it, the reason may be that their internal "terrain," or microenvironment, is hostile to cancer.

Block calls his program Life Over Cancer, and he has some strong ideas about why some people truly beat cancer. In addition to warding off these secondary causes of death, he says, the key factor is making a patient’s internal microenvironment—the biochemical milieu around cancer cells—hostile to malignant cells. Block’s program is aimed at doing that, so that rogue cells that split off from the primary tumor, and that are the chief reasons patients relapse and, too often, die, never take hold. “We have almost completely ignored the environment that cancer sits in,” he told me, “and put all our bullets toward the cancer itself, even when it’s clear that the microenvironment matters.”

That started to become apparent in the early 1980s, with hints that the presence of inflammatory molecules (as in diabetics who also have cancer) meant a poor prognosis. In the 1990s came evidence that the higher a lung-cancer patient’s blood sugar, the worse the prognosis—again, because something about glucose supports the proliferation of cancer cells, and inflammation seems to make cancer cells less vulnerable to chemo and radiation.

In the magazine story this week, I wrote about several leading oncology researchers who couldn’t get funding for one or another innovative idea (including those that eventually led to Gleevec and Herceptin). Block has had similar experiences. “You get funded by NCI for very narrowly-focused research,” he noted. “The problem is, that’s not biological reality.” There have been no large, controlled studies of these complicated interactions between aspects of the internal microenvironment and the march of malignancy.

Despite hints from small studies that breast-cancer patients, for instance, can cut their risk of dying of their disease by 50 percent if they stay fit and are not overweight, says Block, ‘there was almost no funding in this area in the 1980s and 1990s,” and little more now.

Instead, the support goes to research aimed at finding the next chemo. “This kind of focus reflects the magic-bullet mindset of cancer care,” says Block. “We’re so focused on the single defect or disruption [that can mortally wound a cancer cell] because it’s easy to do that research. The Achilles heel mindset, that if you hit cancer in one place the whole thing will come tumbling down, is why we haven’t gotten further.”

Studies that do not fit the Achilles heel paradigm are especially tough to get funded. Block gives the example of pairing the herb astragalus with the mainline chemo drug oxaliplatin, which seems to improve survival in lung-cancer patients. A 2006 analysis of 34 clinical trials of herbal formulas containing astragalus found a 34 percent improvement in the response to chemotherapy and 33 percent reduction in the risk of death among patients receiving astragalus. Yet don't expect to see a large-scale, definitive study of this or any other herbal anytime soon. 

Other proposals in integrative care have also been dead on arrival. In 1997 Block and his colleagues proposed a study on the effects of vegetarian diets in breast cancer. In 2002 they proposed one on an integrated program of diet/fitness/stress reduction for prostate cancer patients. In 2006, they proposed studying how fish oils affect the microenvironment. In 2007, they proposed a pilot study of a diet/exercise/stress management program for breast cancer patients receiving chemotherapy. In every case, no go, even though preliminary studies suggested that these interventions might make a big difference in patients' microenvironment and therefore on their chancer of surviving cancer.

“They did not receive funding for a variety of reasons,” Block told me, “but mainly they were considered too ambitious--an obvious problem with multi-dimensional interventions, at least for reviewers who are accustomed to study designs that are very simple, one dimensional and reductionistic) We have had a number of conversations with staff members at NIH who explained that they are very reluctant to fund studies that involve complex or multi-component interventions because they are considered difficult to interpret scientifically.”

Block continued: “The fact is, our research system is great at studying what we know how to do easily. But it does not necessarily get us the results we need. So, instead of changing the system, we stick with it and keep repeating it over and over and over again.”

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.