June 11, 2021
What will success look like in the war on cancer?
11 June 2021
What will success look like in the war on cancer? When we begin with the end in mind, it
helps us focus on what we want to achieve, understand better how this success can be
attained and create processes to do so. The goal of our strategic plan is to reduce US
cancer deaths from the present 600,000 per year to 100,000 per year by 2030. But how will
this happen?
Historically, medical success has three phases. First, there is a long period of increasingly
greater understanding of the disease and discovery of new treatments and prevention
measures but with a limited improvement in death rates. Later, refinement and coordination
of these new treatments and a better understanding of prevention measures cause dramatic
improvements in the death rate. Finally, with treatment largely successful and prevention
more effective, there are only small improvements in the death rate and a focus on reducing
the side effects of treatment.
Our success in treating HIV / AIDS illustrates these three phases. The blue line below shows
increasing deaths from 1981 (when it was first discovered) to 1995, followed by a dramatic
drop in deaths through 1997, followed by a small decline, see MMWR 2011. Of note, the
drop in deaths is due not only to improved treatment, but also to a reduced incidence of HIV /
AIDS due to more effective prevention activities. Without treatment, most patients die within
10-15 years from exposure (Lancet 2000).
For childhood leukemia, there were also three phases in treatment success, as shown by the
graph below of deaths in England and Wales, see Shaw 2007. The death rate increased until
the early 1960’s when the relative 5 year survival was close to zero, then decreased
dramatically until the late 1990’s when the relative 5 year survival rate was 70-80%, and has
since flattened out. For childhood leukemia, there is no known cause or prevention strategy.
Incidence has risen slightly, for unknown reasons.
For cancer in the United States, the leading causes of death are lung cancer, colorectal
cancer, pancreatic cancer and breast cancer, which together account for 277,210 (45.6%) of
the 608,570 projected cancer deaths in 2021. To reach our goal of only 100,000 annual
deaths, there will need to be major reductions in the cancer death rates at these sites.
Deaths in 2021 (projected) and 5 year relative survival
1 Lung cancer 131,880 21%
2 Colon cancer 52,980 65%
3 Pancreatic cancer 48,220 10%
4 Breast cancer 44,130 90%
5 Prostate cancer 34,130 98%
6 Liver cancer 30,230 20%
7 Leukemia, including AML 23,660 64%
8 Non Hodgkin lymphoma 20,720 73%
9 CNS tumors 18,600 33%
10 Bladder cancer 17,200 77%
11 Esophageal cancer 15,530 20%
12 Kidney cancer 13,780 75%
13 Ovarian cancer 13,770 49%
14 Uterine cancer 12,940 81%
15 Myeloma 12,410 54%
16 Skin 11,540 93% (melanoma)
17 Stomach 11,180 32%
18 Oral cavity & pharynx 10,850 66%
19 Soft tissue 5,350 65% (a)
20 Gallbladder 4,310 19% (b)
Sources: Cancer Facts & Figures 2021, Tables 1, 7 and 8, (a) Cancer.org, (b) Cancer.org.
For the past 70 years we have been slowly accumulating new knowledge with small
improvements in treatment and minor reductions in overall cancer deaths, but at some point,
these improvements will coalesce into substantial reductions. Our strategic plan focuses on
reducing gaps in important knowledge and increasing collaboration of research activities to
get to the “dramatic improvement” phase.
Other processes, including the development of cancer, also follow these three phases.
During the malignant process, our cellular networks slowly accumulate minor variations with
no apparent clinical or microscopic changes. This is followed by bursts of activity leading to
obvious premalignant or malignant changes (Cross 2016). Once malignant, the cancer may
become more aggressive (dedifferentiation) or accumulate only minor changes. Similarly, in
evolution, the theory of punctuated equilibrium describes prolonged periods of apparent
stasis (i.e. no new species) followed by bursts of new species (Eldredge & Gould 1972).
During the “quiet” periods and after the “burst” phase, minor changes in the genetic code are
accumulating, albeit without being noticed.
The theory of self-organized criticality, which also describes earthquakes and stock market
crashes, helps us understand these phases (Bak, How Nature Works 1999). Many
systems, both biologic and sociological, are networks poised at a critical state in which small
disturbances typically cause no network changes, occasionally cause small network changes
and rarely set off a cascade of changes in the initial network and those it interacts with. By
analogy, individual grains of sand dropped on a sandpile usually have no apparent impact,
occasionally cause small avalanches and rarely cause the entire sandpile to collapse.
Dropping a single grain of sand with no apparent impact causes small structural changes in
the sandpile that ultimately may enable an additional grain to set off an avalanche. According
to Kauffman, these “minor” changes build up connections between elements in the network
until a “phase transition” occurs in which so many connections exist that the network
elements act together as a whole, instead of as individual elements. When a large enough
number of “reactions” are catalyzed, a vast web of reactions will suddenly crystallize and
produce dramatic change (Kauffman, At Home in The Universe, page 58).
For cancer research, individual researchers typically study short segments of the “web” of
activity that constitutes cancer. When enough segments are understood, and there are
enough connections made between their work, we anticipate that this web of collaborations
will produce an explosion of new ideas and more effective treatments.
In contrast, the theory of gradualism proposes that major changes occur due to the steady
accumulation of small changes that produce visible differences. Gradualism is logical and
predictable and was promoted by Darwin (Gould 1983), but it does not accurately describe
evolution, malignant progression or the resolution of disease (Sun 2018).
The acceleration of prevention activities will also reduce cancer deaths, but this typically has
a long lead time. For cigarette smoking, one of the most important preventable causes of
cancer deaths, reductions in lung cancer deaths in men, only began 20 years after the
groundbreaking Surgeon General’s Report on Smoking and Cancer.
Source: American Cancer Society
Knowing what success in the war on cancer is likely to look like, we can continue to
emphasize the attainment and accumulation of small successes and collaboration between
scientists, instead of relying on the discovery of a miracle drug or treatment.