Strategic plan to substantially reduce cancer deaths
Nat Pernick, M.D.
Nat@PathologyOutlines.com
27 August 2021
This strategic plan aims to reduce annual cancer deaths in the United States from 600,000 projected in
2021 to 100,000 by 2030. Focusing on reducing cancer deaths will help us determine what needs to be
done and what needs to be better understood.
This strategic plan is updated regularly - click here for the initial version from February 2021. To our
knowledge, it is the only strategic plan intended to substantially reduce cancer deaths. There is no
guarantee of success, but as President Teddy Roosevelt stated, it is important to “dare greatly” (“The
Man in the Arena”, 1910, retrieved 31July21) and attempt to achieve our actual goals, even if we do not
know precisely how to do so. Our strategic plan thus differs from “challenge goals” based on “applying
known interventions broadly and equitably” (Ma 2019).
We need a strategic plan based on reality. Thus, we should stop talking about “a world without
cancer” (American Cancer Society Mission Statement, accessed 27Aug21). Cancer will always be with
us because (a) it is part of the tradeoff inherent in the design of multicellular organisms; (b) we cannot
eliminate random chronic stress, which is a major contributor to lung cancer (How Lung Cancer Arises,
Based on Complexity Theory 2021) and pancreatic cancer (How Pancreatic Cancer Arises, Based
on Complexity Theory 2021); and (c) we cannot totally eliminate personal behavior that promotes
cancer, such as tobacco use and excess weight (Curing Cancer Blog - What should our national
cancer goals be?).
US CANCER DEATHS FROM 1970 TO 2020
Our strategic plan must also acknowledge that, even optimistically, cancer deaths cannot be reduced to
zero. Patients will die of cancer due to treatment refusal, compliance issues, medical conditions which
interfere with treatment, treatment error, treatment failure for unknown reasons and the development of
additional cancers.
The continued high number of US cancer deaths can be viewed as a management problem that requires
that we optimize each step of cancer’s clinical pathway, as indicated below.
1. We should focus on aggressive cancers that cause the most cancer deaths.
To reduce US cancer deaths by 500,000 per year, we must focus on the leading causes of cancer death,
namely most cancers of the pancreas, lung and liver and aggressive cancers of the colon, breast and
prostate (What will success look like in the war on cancer?).
2. We must make our prevention programs more effective.
Between 30-50% of cancer deaths can be prevented by dramatically reducing tobacco use, excess
weight and lack of cancer screening, avoiding other risk factors and implementing existing evidence
based prevention strategies (World Health Organization, accessed 23Aug21).
* We should promote a national program, such as the American Code Against Cancer, that promotes a
culture of being healthy and reducing risk factors.
* States, local governments, nonprofits, the business community and individuals should develop,
implement or support their own cancer action plans.
* We must optimize access to medical care that reduces cancer deaths. This includes providing this care
to needed patient populations and reducing disparities based on race or ethnicity, region of residence and
socioeconomic status (Ma 2019, Michigan Cancer Plan 2021-2030).
3. We must develop better screening programs for cancers with high mortality.
This includes early detection of lung, pancreatic and liver cancers, detection of aggressive colorectal,
breast and prostate cancers and life threatening second cancers in those currently being treated
(Zaorsky 2017). We should study whether screening for chronic inflammation associated with many
cancers is useful and if so, how best to do it.
4. We must reduce cancer deaths that occur shortly after diagnosis.
Some cancer patients die shortly after diagnosis due to treatment side effects, based on treatment aimed
at killing all cancer cells as quickly as possible. However, focusing instead on managing cancer may
actually be more important and the aggressiveness of treatment should be balanced against patient risk
(Huang 2014). In addition, some patients with cancer die of infections shortly after diagnosis, which
should be anticipated and prevented (Zheng 2021, Van de Louw 2020). Finally, we speculate that
although many patients have advanced disease at diagnosis (McPhail 2013, Suhail 2019), some die
primarily due to disruptions to essential physiologic networks and not due to cancer related destruction of
essential organs (Zaorsky 2017). We should investigate cancer deaths that occur shortly after diagnosis
to determine what physiologic pathways are involved and to create treatment protocols to counter these
changes, similar in concept to creating protocols to treat new onset diabetes presenting with life
threatening ketoacidosis (Curing Cancer Blog - Part 9).
5. For each cancer site and histologic type, we should compile a list of partially effective
treatments and promising malignant attributes to target.
We speculate that for each cancer histologic type, even the most aggressive, there exists a combination
of perhaps 8-10 therapies that individually may be only partially effective but together can be substantially
effective (Curing Cancer blog - Combinations of Therapy).
Life is based on principles of complexity science: the behavior of the whole is greater than the sum of the
behavior of the parts. These extra properties are due to interactions between the parts which are often
unpredictable. Each specific type of cancer is caused by behavioral risk factors or random events that
cause small network changes that slowly percolate across adjoining networks and cause them to change.
Eventually, the accumulation of these small changes may produce bursts of major changes that cause
premalignant conditions and additional bursts may cause overt cancer. Due to the complicated nature of
these network changes, no simple therapy can eradicate all cancer cells and restore order to the large
number of altered networks. We need a large number of drugs to successfully damage the weblike nature
of the malignant process (Palmer 2019, Ayoub 2021).
The set of therapies to choose from may need to total 30 or more, which totals 6 to 30 million
combinatorial possibilities. Using machine learning, cell lines and animal models may be helpful to
choose which combinations will be most effective (He 2021, Kim 2021, Paltun 2021). Traditionally, most
therapies target the “hallmarks of cancer” (Hanahan 2011), particularly cell division. However, we believe
it important to also target other biologic networks, including:
* Networks that promote a microenvironment that nurtures cancer cells at primary and metastatic sites,
including vasculature, stroma, extracellular matrix and inflammation (Pancreatic Cancer Treatment
Targets, Curing Cancer - Part 6 - Key systemic network issues).
* Systemic chronic inflammation, often low grade and associated with cancer risk factors (How cancer
arises from chronic inflammation, based on complexity theory).
* Systemic hormones (estrogens, androgens, insulin) that promote cancer in the breast, uterus, prostate
and pancreas.
* Ineffective immune system networks that coevolve with carcinogenesis.
* Germline changes that promote malignant behavior.
* Risk factors, both behavioral and non-behavioral, particularly those likely in the short term to promote
inflammation, affect hormonal levels or impair the immune system.
6. Suggested therapeutic strategies include:
* Target dysfunctional networks, not just specific mutational changes.
* Consider combinations of 3-5 drugs to attack the biologic web that supports each malignant attribute.
* Since treatment typically does not kill all cancer cells, it is important to move surviving cancer cells into
less hazardous networks (Curing Cancer - Part 5 - Key network issues that affect the primary
tumor), termed communicative reprogramming (Heudobler 2019) or metabolic reprogramming (Li 2019).
* Monitor the status of systemic networks promoting the malignant process before and after treatment.
* Treatment should focus on managing the malignancy to reduce death and disability, not eliminating
every possible cancer cell.
* Consider achieving “marginal gains” at all steps of the disease process (Powell-Brett 2021), which may
increase possible treatment options and reduce a sense of futility (Curing Cancer blog – part 9 – How
cancer kills).
* Therapy should be patient centered to the extent possible because patients may have markedly different
therapeutic preferences.
* Aggressively enroll patients into clinical trials so physicians can learn and improve over time.
Additional resources:
* Follow our Curing Cancer Blog at https://natpernickshealthblog.wordpress.com/ .
* Sign up for our Curing Cancer Network monthly newsletter at
https://lp.constantcontactpages.com/su/onz6IND .
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