Some historians have argued that the war on cancer was, in part, a stealth effort by President Nixon to rein in the independence of medical scientists by creating a federal structure through which the executive branch would exert some control over their funding. Others hold a less cynical view, believing that the war ushered in a restructuring of clinical cancer research, replacing what had been, until then, an unfettered approach to cancer medicine in which investigators would be free to test some fairly outlandish theories at the bedside without encountering interference from regulatory bodies.3
Four decades forward, it was President Barack Obama’s turn to launch his war on something.
Discarding the bellicose terminology of his predecessors, President Obama chose a more soothing moniker, the Precision Medicine Initiative, to describe his vision for “a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge and therapies to select which treatments will work best for which patients.”4 All rainbows and sunshine. It seems that this mellow approach failed to trigger the widespread excitement that the White House had anticipated.
At his final State of the Union address this past February, President Obama relaunched the effort by rebranding it a National Cancer Moonshot, to be led by Vice President Joe Biden, whose goal is to achieve “a decade’s worth of advances in five years.”5 Lesson learned. Precision, initiative, these are words that belong in PowerPoint presentations. Moonshot—now that’s a term to rally the troops!
The War Against Autoimmunity
If one decides to wage war against a disease in the hopes of stirring the public sentiment, choosing cancer as the target will invariably garner the most attention. Politicians are not the only ones who are keenly aware of this reality.
Every weekend this past winter, I met hundreds of charity-sponsored runners running along my beaten trail, the Heartbreak Hills of Newton, Mass. Nearly all were training for the Boston Marathon and most had qualified, not by having completed a prior marathon at a grueling pace, but by pledging to raise thousands of dollars on behalf of a particular illness. Hands down, these pledges nearly always were in support of cancer research: breast, brain, colon, pancreatic, prostate, liver, lymphoma, retinoblastoma—the list was endless. Cancer seizes our attention unlike any other disease. And it terrifies us, unlike any other disease.
Fortunately, rheumatologists and their patients have benefited from some of the seminal discoveries made during the course of the war on cancer. Among the most consequential breakthroughs was the elucidation of the role of tumor necrosis factor (TNF) in the mediation of autoimmunity and inflammation (see “A Short History of RA Therapeutics,” The Rheumatologist, January 2012). The name tumor necrotizing factor was first coined in 1962 to describe sarcoma regression activity induced in the serum of mice treated with Serratia marcescens polysaccharide. This endotoxin-induced serum factor that caused necrosis of tumors was elegantly characterized by researchers at the M.D. Anderson Cancer Center in Houston.6 Due to its highly potent pro-inflammatory effects, efforts to harness TNF as a systemic therapy met with failure. However, evidence was mounting that TNF served key roles in non-cancer pathways, in particular, sepsis and shock.
Distinct from prior immune therapeutic agents, which primarily boost systemic immune responses or generate de novo immunity against cancer, anti-PD-1 therapy modulates immune responses at the tumor site, targets tumor-induced immune defects & repairs ongoing immune responses.
The focus then shifted to developing a treatment for overwhelming infection by creating antibodies targeting TNF, but after a series of experiments failed to demonstrate the benefit of these antibodies in protecting mice against the ravages of septic shock, TNF blockade appeared to be headed to the pile of discarded ideas.
