Strategic plan to reduce cancer deaths
Nat Pernick, M.D.
Nat@PathologyOutlines.com
15 June 2021
This strategic plan aims to reduce annual cancer deaths in the United States from the 600,000 projected
this year to 100,000 by 2030. It is updated regularly - click here for the initial version from February 2021.
To our knowledge, this is the only strategic plan for substantially reducing cancer deaths that exists - the
American Cancer Society has a “2035 challenge goal” but not a strategic plan (Ma 2019).
We need a plan based on a target that represents our actual, rational goals, even if we do not know how
to achieve them today. This is different from “challenge goals” based on extrapolations of current trends
with small improvements. We also need a plan based on reality. Thus, we should stop talking about “a
world without cancer” (American Cancer Society Mission Statement, accessed 28May21). Cancer will
always be with us because: (a) it is part of the tradeoff inherent in multicellular organisms, (b) random
chronic stress, 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), cannot be eliminated and (c) personal behavior that promotes cancer, such as tobacco use and
excess weight, also cannot be eliminated (Curing Cancer Blog - What should our national cancer
goals be?).
A realistic cancer plan should acknowledge that cancer deaths cannot be reduced to zero. Some patients
will always 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.
US CANCER DEATHS FROM 1970 TO 2020
This is our strategy for reducing annual US cancer deaths to 100,000:
1. Kill or disable the primary cancer.
Our failure to kill the primary (main) cancer is often due to our reliance on reductionism as the theory of
disease. Reductionism states that the behavior of the whole is equal to the behavior of the sum of the
parts. Thus the reductionist goal for cancer is to find and fix the broken parts. In reliance on this theory,
our medical and political leadership have focused on finding “the cause” or “the cure”. In doing so, they
have compared cancer success to the technological achievements of splitting the atom or landing on the
moon. However, this thinking is misguided.
Life is based on the 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, such as lung adenocarcinoma, is caused by behavioral risk
factors or random events that cause small network changes that slowly percolate across adjoining
networks but eventually produce bursts of major changes. These bursts 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 successfully eradicate the primary cancer, we suggest focusing on these strategies:
* Target dysfunctional cancer networks, not just mutations. Most current investigation focuses on
important cancer attributes, such as rapid cell growth, apoptosis resistance and metastatic spread.
Physicians and scientists discover common mutations in cancers, develop companion diagnostic tests to
identify them and develop drugs that target that mutation. Although the drug may be helpful, it is not a
complete solution (Brock 2017). The mutation occurs in an important network (pathway) for the cancer,
but it represents only one of many alterations possible at each step in this network.
* Consider combinations of 3-5 drugs or other therapies per cancer attribute because each attribute is
part of a web that can bypass a specific block.
* Target multiple attributes of the cancer, which may require combinations of combinations of therapies.
This is important because cancers that appear identical may be caused by different types of mutations or
network alterations and respond differently to treatment.
* Move surviving cancer cells into less hazardous networks through biomodulation (communicative
reprogramming, anakoinosis, Heudobler 2019) or similar strategies. Since treatment typically does not
kill all cancer cells, it is important to have therapy for those cells that survive (Curing Cancer - Part 5 -
Key network issues that affect the primary tumor).
* Be more aggressive in enrolling as many patients as possible in clinical trials so physicians can learn
and improve from each patient.
2. Identify, target and monitor networks that promote malignancy.
Anti-cancer treatment typically focuses solely on the primary cancer. However, adult cancers are due to
risk factors that destabilize networks throughout the body and continuously transform normal cells into
cancer cells. For these reasons, simply eradicating the primary cancer often cannot be curative. Thus, we
recommend these strategies focused on networks outside the primary cancer:
* For each cancer type, identify relevant local and systemic networks that nurture and sustain the
malignant process (Curing Cancer - Part 6 - Key systemic network issues).
* Develop therapies that change these networks so they are no longer cancer promoting.
* Determine how to monitor these networks before and during treatment.
* Confirm that treatment of these networks improves patient survival.
* Consider creating a cancer network score to supplement the TNM score.
Networks currently identified that nurture and sustain the malignant process include:
* Networks that promote a microenvironment that nurtures cancer cells at primary and metastatic sites,
including vasculature, stroma, extracellular matrix and inflammation.
Treatment: attempt to normalize these networks.
* Networks that promote embryonic features associated with aggressive cancer behavior.
Treatment: use agents that promote maturation, such as retinoids (used for acute promyelocytic
leukemia), myeloid differentiation promoting cytokines, other cancer cell reprogramming drugs or
possibly agents that halt rapid cell division in embryogenesis.
* Networks that promote malignant-like unicellular processes instead of stable multicellular processes.
Treatment: activate multicellular networks and suppress unicellular networks. Target cancer cell
weaknesses by applying a specific cellular stress that is readily dealt with by healthy cells using
multicellular programming but not by cancer cells with predominantly unicellular programming.
* Chronic inflammation, often low grade and associated with cancer risk factors or “super
promoters” (How pancreatic cancer arises, based on complexity theory 2021).
Treatment: trigger pro-resolution pathways; use anti-inflammatory agents; mimic physiologic
halting mechanisms associated with wound healing and liver regeneration.
* Ineffective immune system networks that coevolve with carcinogenesis.
Treatment: target alterations to “command and control” aspects of the immune system as well as
the dysfunctional behavior of specific immune cell types.
* Hormones (estrogens, androgens, insulin) for relevant cancers (breast, uterus, prostate, pancreas).
* Treatment: antagonize hormones that may promote cancer growth directly with anti-hormonal
agents or indirectly with behavior changes such as weight loss, exercise, healthy diet and
reducing alcohol and tobacco use.
* Germline changes that promote malignant behavior.
* Treatment: detect by genetic testing of noncancer cells, then normalize these networks or
counter changes that promote instability.
3. Reduce cancer deaths that occur shortly after diagnosis.
Some cancer patients die shortly after diagnosis due to treatment side effects or infections. Treatment
side effects that are life threatening may be due to an unreasonable desire to eliminate all cancer cells as
quickly as possible. Although cancer cell eradication is an important goal of therapy, it need not occur at
the outset and must be balanced against patient risk (Huang 2014). In addition, patients with cancer often
die of infections shortly after diagnosis, which should be anticipated and prevented (Zheng 2021, Van de
Louw 2020). Finally, we speculate that focusing on cancer deaths occurring shortly after diagnosis for
other reasons may be useful. Although many of these patients have terminal disease (McPhail 2013,
Suhail 2019), some may die primarily due to life threatening disruptions to essential physiologic networks
that can be stabilized, comparable to diabetic ketoacidosis. Once stabilized, the patients may have a
longer lifespan, although long term planning to control the cancer is still needed (Curing Cancer Blog -
Part 9, Zaorsky 2017).
Specific goals are:
* For each cancer type, determine the optimal initial treatment to reduce short term, treatment related
deaths.
* For each cancer type, determine the optimal treatment to reduce infection related deaths.
* Investigate cancer deaths that occur within 30-60 days of diagnosis to determine what physiologic
pathways are involved and create treatment protocols to counter these changes.
4. Strengthen public health and preventative programs.
It is important to have a national program supported by local government, nonprofits, the business
community and individuals that promotes a culture of being healthy and reducing risk factors, such as the
American Code Against Cancer and other healthy lifestyle messages.
Specific goals are:
* Prioritize cancers for general screening with high mortality but effective treatment options when detected
early.
* Develop more effective screening programs to identify premalignant or malignant lesions in both high
risk patients and current cancer patients being monitored for relapse.
* Identify the most important screening programs for patients with cancer at risk for second cancers that
are life threatening (Zaorsky 2017).
* Analyze whether testing or treatment for chronic inflammation associated with cancer is useful and if so,
how best to do it.
* Determine how best to improve access to medical care that will reduce cancer deaths and how best to
provide this care to needed patient populations. This includes reducing disparities based on race /
ethnicity, region of residence and socioeconomic status (Ma 2019, Michigan Cancer Plan 2021-2030).
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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