The War on Cancer – Big Promises met with Limited Success

Politicians and leaders often use war as a metaphor for non-combat efforts against formidable foes. In the 1960s the US saw a “War on Poverty” as part of the Great Society program. In the 2000s we saw a War on Terrorism. There have been many Wars on Crime and the War on Drugs. But the biggest failure of any of these was the War on Cancer. This failure is acknowledged by observers who have studied the history. Hundreds of billions of dollars have been spent, much has been learned, new treatments have been devised, but the high-level results have been lacking.

The year 1971 is usually taken as the start of the War on Cancer. President Richard Nixon announced a plan to go after the disease in his State of the Union speech and the Congress voted large increases in funding for the National Cancer Institute. Fueled by the development of new chemotherapy drugs, optimism swelled. Some speakers spoke of a goal of curing cancer by 1976 as a gift to the nation on its bicentennial.  In the 1960s John Kennedy set a goal of landing a man on the Moon by the end of the decade.  It was a huge challenge which American scientists and engineers rose to.  If we can land a man on the Moon, we should surely be able to cure cancer.

That didn’t happen. Cancer proved much harder to tackle than people thought. The deeper biologists looked into the disease, the more complex it was. And cancerous tumors developed resistance to drugs – essentially evolving inside the patient’s body.  Still, there was some limited success and chemotherapy established itself as a tool in the oncologist’s toolbox.   The 1972 Albert and Mary Lasker Prize in Medical Research was given to scientists who demonstrated proof of principle for the cure of cancer with drugs.  Medical oncology was accepted as a branch of medicine in the 1970s.

Basic research (learning the biology of cancer) and translational research (devising ways to fight cancer) was funded as the NCI granted scientific activity in universities and research institutes around the country.  Pharmaceutical companies and biotechnology companies undertook expensive research in the hopes of finding profitable new therapies.  New radiation and surgical techniques were developed and many chemotherapy agents were discovered. Hormone therapy expanded and immunotherapy started.  There were some successes – great progress in raising the cure rates in acute lymphoblastic leukemia in children and Hodgkin’s Disease which often strikes young adults.  Solid tumors proved more difficult as the cytotoxic drugs developed in the 1970s and before had limited efficacy.

In the 1990s people got excited about angiogenesis inhibitors. But they were not miracle cures either. The Human Genome Project of the late 90s was a basic science investigation that people would yield benefits in many areas, including prevention and treatment of cancer. In 2000 US President Bill Clinton proclaimed “future generation will know cancer only as a zodiac sign.”

Into the 21st Century

In 2003 the director of NCI Andrew C. von Eschenbach set a goal of solving the cancer problem by 2015. Citing “exponential growth” in knowledge of the origins and growth of cancers, he said the research community was at a “strategic inflection” point in oncology. He said he thought this was a realistic goal based on input from experts. von Eschenbach pointed to new tools including robotic screens for new drugs and combinatorial chemistry.  He proposed a “seamless 3-D approach” The three Ds were discovery, development, and delivery. “Discovery” in this context was not drug discovery, but basic research: figuring out the origin and growth dynamics of cancer at biochemical level. “Development” referred to a wide range of activities, encompassing creation of methods to prevent, detect, diagnose, and treat cancer. “Delivery” was about getting the tools out to the nation down to local doctors’ offices and community clinics.

By 2015 there was no cure for many cancers, and cancer was still the second-leading cause of death.   There were successes.  Epidemiologists have calculated that the age-adjusted cancer mortality rate fell 27 percent between 1990 and 2015 in the US.  (Overall cancer mortality hasn’t fallen that much because of the aging of the population.) Some of this decline in mortality is due to risk reduction (decline in smoking) and earlier detection. But however you cut it, the successes have not been nearly as dramatic as promised or hoped.

The federal government started a Precision Medicine Initiative in 2016 with an initial focus on cancer.

Hope continues to spring eternal. Precision medicine, immunotherapy advances, new biochemical targets beckon. It is all hype? Time will tell. There has been skepticism about the grand claims of precision medicine advocates. Writing in The Atlantic in 2016, historian Nathaniel Comfort worried about “the heady sense of impending omnipotence that accompanies major technological and scientific advances.”  The pharmaceutical companies have developed dozens on anti-cancer medicines in recent years, but progress against the disease has been slow.  In the 1990s 30 new oncology drugs were approved by the FDA.  In the 2000s the number was up to 35, and in the 2010s it was 103.  The sheer quantity of new drugs would amaze scientists and doctors working in the 1970s.

Software company Microsoft announced a plan to “solve” cancer in 2016.  By approaching it as a computing problem, they thought that the new approach would let them make inroads where biology and medicine had failed.  A newspaper article described the company’s strategy a “tackling cancer as if it were a bug in a computer system.” A scientist on the project predicted success “for some of the cancers five years, but definitely within a decade. Then we will probably have a century free of cancer.”

As part of the US government’s 21st Century Cures Act, a bill passed by Congress in 2016, the National Cancer Institute started the Cancer Moonshot – an attempt to make more rapid progress.

Why is it so hard?

Curing cancer turned out to be harder than landing a man on the Moon, which many in 1971 may have found surprising.  Cancer turned out to be a devilishly difficult disease to understand and to stop.  Plenty of money has been spent.  The National Cancer Institute had a budget in Fiscal Year 2021 of $6.56 billion, up from $400 billion in 1971.  The equivalent of the NCI in other countries also funds basic and translational research.  Even some state governments in the US fund cancer research.  Private industry has also invested billions.

Medicine has made considerable progress in some areas since the early 1970s.  But cancer, which is a disease at the deepest level of biology, remains elusive.  There have been successes to be sure. but we have a long way to go.

Converting Cancer to a Managed Disease

If we can’t cure cancer, maybe we can tame it enough to allow us to live with it.  In 2009 Nature published an article called “A change of strategy in the war on cancer.”   The author, Roger A. Gatenby, advocated a switch from trying to cure cancer to trying to control it.  Pointing out that harsh treatments reduce the patient quality of life, often do not eliminate the cancer, and may even make the cancer worse (by forcing evolution of the tumor inside the body), and promoting resistance to the treatment, he suggested adoption of a system similar to integrated pest management used in insect control.

Many diseases are like this. Malaria, diabetes, are diseases people have for decades. They can be fatal and they often do contribute to the person’s death. But they are not a short-term death sentence when first detected so long as people start treatment.

It’s more or less the difference between a chronic condition and an acute disease. Some cancer cases are already like this. They are either naturally slow-growing malignancies or they are slowed through medical treatment, but never really cured. Indeed, medical providers resist using the word “cure” even for patients with great results, instead using the word “remission”.  This is partly to control hopes and expectations among the patient and family.  And it is true that often a cancer that has gone to remission will re-emerge years later.

chemo patientThe cancers that do come back shorten life expectancy – can we work on those to make them less fatal? Say turn a disease that normally kills patients 2 years after diagnosis and turn it into a disease that the patient can survive for 20 or 30 years? Perhaps this could be done with chemotherapy – existing or new drugs – and a metronomic regimen.

Another way of looking at this is: is the cancer stable or progressing? If it is stable and the patient can function, that might be the best we can hope for. If it is progressing, the cancer is growing and make lead to worsening patient condition, but even then if the progress is slow enough, the extra lifespan the medical intervention provides can be useful and appreciated.

The search for a cure for cancer has proven quixotic, so maybe recalibrating our expectations is a wise course.

See also: history of chemotherapy