Our Long War on Cancer
Regina Kelder

Our Long War on Cancer

When President Nixon declared war on cancer in 1971, the arsenal included radiation and a handful of chemotherapy drugs. But the preferred weapon was the scalpel, not just to remove tumors but to diagnose disease. (This was, in fact, how doctors discovered, in 1977, the malignant tumor on my mother’s pancreas; by opening up her chest and going on an exploratory, fact-finding mission.)
Today, the battlefield looks much different. The chemotherapy war chest has grown tremendously. There are now around 150 cancer and oncology drugs licensed by the US Food and Drug Administration—from standard chemo regimens to targeted therapies that interfere with a tumor’s machinery —and a remarkable 850 candidates in clinical trials, according to the Pharmaceutical Research and Manufacturers of America. And that’s just on the drug side. Advances in radiation and computer technology have made it possible to aim radiation more precisely and to even deliver it at the time of surgery. Monoclonal antibodies that target specific tumor antigens and cancer vaccines that boost the body’s immune system have been added to the stockpile. Surgical techniques are more sparing and diagnostic tools more refined.

So one would think that this enormous military we have assembled—and the billions spent every year on cancer research—would have led to a cure for cancer. That certainly was the intention of the National Cancer Act when Congress authorized it in 1971 and boosted federal funding.

But 42 years later scientists are still knee-deep in the ground campaign, and while there has been much progress in the treatment of cancer, some wonder whether our current defensive strategies are in need of some serious—and novel—reinforcements. That’s certainly the opinion of Clifton Leaf in his much-discussed book, “The Truth in Small Doses: Why We’re Losing the War on Cancer and How to Win It.” Leaf, who is not a scientist but is a cancer survivor, argues that the 1.6 million Americans who are diagnosed with cancer every year—and the 600,000 who are expected to die from it—is not evidence of a winning campaign. He suggests that too much money—and attention—is being spent on finding new treatments to cure this incredibly complex disease, rather than on finding ways to prevent it or, at least, keep it from progressing. He also thinks the field needs to be bolder in the research projects it pursues.

Leaf is not the first one to ponder these questions, and not everyone shares his opinion that the field has become too static, that scientists are too risk-averse. (In today’s uneasy funding climate, who can blame them?) To be sure, there have been many solid advances in the prevention, diagnosis and treatment of cancer—including some of the deadliest—while mortality rates from cancer have been on a steady decline for two decades. We’re also catching more cancers during the earliest stages.

Yet cancer refuses to succumb. It remains the second-leading cause of death in the U.S. behind heart disease; about half of men and one in three women will develop cancer at some point in their life, according to the American Cancer Society. So as we kick off a month that is filled with almost constant reminders about the most common cause of cancer in women—and a Eureka series devoted to cancer—one could and should ask why it’s been so difficult to translate the findings from in vivo and ex vivo research models into new tools and drugs in the clinic; and what the field needs to do differently to get the job done.
Tweaking the models
Cheryl Marks, who oversees the Mouse Models of Human Cancers Consortium at the US National Cancer Institute—a decade-long effort created to develop models that parallel the ways that human cancers develop—says we have actually learned a lot about the biology of cancer from animal models.  Studies have shown that when animals “representative” of a certain subset of cancer patients receive the standard chemotherapy regimen, some respond, some resist and some see a recurrence, which is essentially what occurs in people.

What our animals haven’t been able to tell us, she says, is how to overcome metastatic disease. Marks thinks the field needs more robust tumor models that really mimic the late-stage cancers responsible for most of those 600,000 cancer deaths.  She also thinks the field hasn’t used animal models as effectively as it could to study patterns of drug resistance.

And Marks says the field could also benefit from a better suite of early cancer models that might enable the development of translatable serum biomarker signatures. Such markers could be useful litmus tests for how indolent a cancer is. Marks says a consortium member recently published a study showing that a signature developed in a mouse was predictive of indolent prostate cancer, though its reliability as a surveillance tool would need to be validated in a clinical trial.

Despite the challenges in using mice to study the natural history of cancer, Marks doesn’t think we should dispense with animal models.  “But we certainly are promoting more collaborations across the research community who model in a variety of systems, including in silica (nanoparticles),” she says. “This way we can end up pulling the very best animal data and cell line data into computational models.”

At the end of the day, beating cancer may come down to less of a ground game and more of a drone attack.  Researchers have come to realize that one of cancer’s biggest weapons is its heterogeneity.  Cancer is not a single entity, but more than one hundred complex and distinct diseases, with most cancer types demanding a unique treatment strategy.

Consider breast cancer. It’s not one disease but at least a dozen different diseases.  What troubles oncologists is that if you treat any one these categories of breast cancers, there will be subgroups of women who respond to treatment and those who do not.

So it makes sense to have genetic tools that might help predict whether a tumor will return so that doctors can advise their patients of the best treatment.  Chuck Harrison, Senior Research Director at Charles River Discovery Services in North Carolina and a 40-year veteran of cancer drug discovery will talk about why it’s so important for patients to advocate for these tests in an upcoming blog that will be part personal—his wife is a 13-year breast cancer survivor.  We’ll also be featuring a blog from Charles River toxicologist Kristina York, who works at our Reno, Nevada lab, about the power and challenges of monoclonal antibodies—a growing presence in cancer immunotherapy since the FDA’s approval of Herceptin in 1998. And we’ll feature a guest blog about the launch of the Cancer Genome Atlas and its companion project, Pan Cancer that will hopefully yield fresh insights into cancer development and behavior.

Which brings me back to my mother’s battle. Despite the dismal prognosis, she reluctantly agreed to single-line chemotherapy.  As predicted, she died within months of her prognosis. But the remarkable thing was that she responded surprisingly well to the drug; the tumor on her pancreas shrank dramatically.

Which begs the question, what might we accomplish if we could use all these preclinical and clinical tools to customize treatment and outfox the disease?