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Strategic plan to substantially reduce cancer deaths

Author: Nat Pernick, M.D.

Last revised: 1 June 2023
See our blog for additional discussions

This strategic plan, created in February 2021, aims to substantially reduce cancer deaths in the United States from the 600,000 deaths projected for 2022 to 100,000 per year. After 50 years of fighting the War on Cancer (NCI: National Cancer Act of 1971, accessed 15May23), we need to "dare greatly" (The Man in the Arena 1910, accessed 15May23) to determine our desired cancer related goals (Pernick: Let's cure cancer together 2021) and how we might attain them, even if many steps are unknown. Thus, our strategic plan differs from "challenge goals" that are based on "applying known interventions broadly and equitably" (Ma 2019).

This strategic plan to substantially reduce cancer deaths is essentially a management plan to use all of the treatment and public health approaches possible that may impact cancer deaths (Pernick: Curing cancer - Curative cancer treatment based on complexity theory 2022). We will not be successful by focusing on a silver bullet or other miracle treatment that might theoretically solve all of our problems (Pernick: What should our national cancer goals be 2022). Instead, success will likely arise from an expanding number of modest improvements with occasional bursts of major advances (Pernick: What will success look like in the war on cancer 2021).

We should be honest about what we can and cannot do. As the American Cancer Society has now recognized, we cannot achieve a world without cancer. Cancer will always be with us because (A) multicellular organisms are based on self-organized critical states with a predictable risk of catastrophic system failure in the form of cancer (Pernick: The Laws of Complexity and Self-organization: A Framework for Understanding Neoplasia 2017); (B) we cannot eliminate personal behavior that promotes cancer, such as tobacco use and being overweight (Pernick: How Lung Cancer Arises, Based on Complexity Theory 2020, Pernick: How Pancreatic Cancer Arises, Based on Complexity Theory 2021); and (C) we cannot eliminate random events, a major contributor to lung, pancreatic and other cancers (Pernick: Curing cancer - Random chronic stress / bad luck as a major cause of cancer 2022).

In addition, even with curative treatments available, cancer deaths cannot be reduced to zero; therefore, proposing a goal of a very small number of deaths is not sensible. Many patients will still die from cancer due to treatment noncompliance, medical conditions that interfere with treatment, treatment error, treatment failure for unknown reasons and the development of additional cancers.

Our specific strategies are

1. Treatment should target as many individual biologic networks as possible that contribute to the cancer itself, directly or indirectly, and our public policies must optimize all aspects of our healthcare system that affect cancer deaths.

Cancer arises in individuals due to multiple disruptions to interacting biological networks. These networks are physiologically at a tipping point that may lead to more chaotic, premalignant states (Pernick: Strategic plan discussion #3 2023) but typically maintain resistance against change through redundant control systems (Pernick: The Laws of Complexity and Self-organization: A Framework for Understanding Neoplasia 2017). Chronic disturbances affecting different aspects of the networks may ultimately overcome these controls and produce premalignant or malignant cells that acquire their own type of stability (cancer attractors) that are resistant to change (Huang 2009). For individual patients, we will need treatment consisting of multiple disruptions to cancer networks and other systemic networks that nurture the malignant process and constitute an altered systems biology. At a societal level, we will need improvements in our healthcare system regarding prevention, reducing healthcare disparities and making treatment more available.

2. Successful treatment will likely require combinations of combinations of therapy, each attacking a different aspect of the malignant process.

  • Childhood leukemia is curable using combinations of therapies that target cancer cell growth (Pomeroy 2022). Treating adult solid cancers should build on this success by using combinations of therapy to target all aspects of the malignant process:
    • Kill as many cancer cells as possible using multiple, distinct methods to address cancer cell heterogeneity (de Sousa 2018, Punt 2017)
    • Attack multiple targets within each network because biologic pathways are weblike, not linear, allowing cancer cells to bypass important steps blocked by anticancer agents
    • Target the microenvironment that nurtures cancer cells at primary and metastatic sites because cancer cells require a fertile soil for the cancer seeds to grow (i.e., target the vasculature, inflammatory cells and their products and the extracellular matrix or cellular infrastructure)
    • Disrupt the chronic inflammation produced by many risk factors that promotes the malignant and metastatic processes
    • Antagonize hormones that promote cancer cell growth
    • Counter cancer associated immune system dysfunction
    • Identify and target genetic changes associated with cancer promotion
  • Successful treatment plans may also involve moving cancer cells that survive treatment into less aggressive networks (Pernick: Curative cancer treatment based on complexity theory 2022, Pernick: How Lung Cancer Arises, Based on Complexity Theory 2021).
  • We speculate that for each cancer type, even the most aggressive, there may exist combinations of 10 - 15 therapies that individually may be only partially effective but together can be substantially effective in reducing cancer deaths (Pernick: Strategic plan discussion #4 2023). No single therapy is likely to eradicate most adult cancer cells and restore order to the large number of networks altered during the malignant process. We may need to develop 30 or more partially effective therapies to choose from (Pernick: Pancreatic cancer update 2021) and use machine learning, cell lines, animal models and ultimately clinical trials to test the huge number of potential combinations.

For long term success, we must also reduce the chronic cellular stressors or risk factors that promoted the original cancer (Pernick: How Cancer Arises Based on Complexity Theory 2017) and will continue to promote premalignant and malignant conditions unless stopped.

3. We should initially focus on aggressive cancers that cause the most cancer deaths.

From a management perspective, we should initially focus on the major causes of cancer deaths, namely most cancers of the lung, pancreas and liver as well as aggressive cancers of the colon, breast and prostate (Pernick: What will success look like in the war on cancer 2021). We should study whether strategies to substantially reduce cancer deaths at these sites may be applicable to other sites.

4. We should reduce cancer deaths that occur shortly after diagnosis.

Many patients with cancer die within one year of diagnosis, which can be attributed to noncancer causes, including cardiovascular disease and suicide (particularly with multiple primary cancers, Su 2022), treatment, infections and respiratory disease (Yang 2021). Although some of these patients have advanced cancers at diagnosis (McPhail 2013, Suhail 2019), we speculate that some of these deaths are immediately due to cancer related alterations in essential physiologic pathways, both known (Lewis 2011, Baralo 2023) and unknown, which can be countered using treatment available today; this is analogous to treating new onset diabetes presenting with life threatening ketoacidosis (Pernick: Curing cancer - How cancer kills 2022).

In addition, we can reduce early treatment related cancer deaths by focusing more on managing cancer instead of killing all cancer cells (Pernick: Curing cancer - Curative cancer treatment based on complexity theory 2022, Huang 2014, Surh 2021) and by better anticipating and treating infections that often kill cancer patients (Zheng 2021, Van de Louw 2020).

5. We should incorporate therapeutic strategies that delay cancer deaths.

We can prolong the lifespan of patients with cancer by achieving marginal gains at all steps of the disease process (Powell-Brett 2021). In addition, honoring patient therapeutic preferences may alleviate symptoms and overall distress (Balogh 2011, Tsvitman 2021). These strategies may increase possible treatment options and reduce the sense of futility or nihilism associated with cancer deaths (Pernick: Curing cancer - How cancer kills 2022).

6. We should focus on reducing age related cancer deaths.

The incidence of most malignancies increases exponentially with age during adulthood (Benz 2008). More than two - thirds of invasive cancers occur at age 60 years or older (White 2019) and advancing age is the most important risk factor for cancer overall and for many individual cancer types (Pernick: How Cancer Arises Based on Complexity Theory 2017). Since US cancer incidence is projected to increase by almost 50% in 2050 due to population growth and aging, a greater emphasis on cancer risk reduction is needed (Weir 2021).

7. We should attempt to enroll every patient in a clinical trial so physicians can learn and improve.

Clinical trials typically compare the current standard therapy for a particular risk group with a potentially better treatment that may improve survival or reduce treatment side effects. They are particularly important to test whether treatment combinations will be effective and tolerable in different patient groups (Pernick: Curing cancer - Adult versus childhood cancer 2022). Enrollment in US cancer treatment trials is 6.3%, increasing to 18.9% at National Cancer Institute designated comprehensive cancer centers (Unger 2021). Although higher than previously thought, this means that most patients are NOT part of a clinical trial. To attain substantial reductions in US cancer deaths, we must take the administrative steps necessary to attempt to enroll every patient with cancer in a clinical trial. Once done, we will better understand the challenges to treatment success due to age, ethnicity, socioeconomic status and other factors.

8. We should make our prevention programs more effective.

Between 30% and 50% of cancer deaths can be prevented by dramatically reducing tobacco use and excess weight, improving our diet (adding more non-starchy vegetables, fruit, fiber and whole grains and reducing fat, sugar and processed food), reducing alcohol use (particularly heavy, long term use and binge drinking, LoConte 2017, Strebel 2021), increasing vaccinations against HPV and Hepatitis B, treating infections and infestations that predispose to cancer (Plummer 2016, de Martel 2020, Pernick 2021a), reducing other risk factors and implementing other evidence based prevention strategies (World Health Organization, accessed 26May23, GBD 2019 Cancer Risk Factors Collaborators 2022). This also includes targeting risk factors that are important for only specific cancer types, such as nonuse of screening for colorectal cancer (Pernick 2020).

Reducing even a single risk factor is important because a combination of multiple risk factors are typically needed to promote the malignant process, so eliminating one may halt it. Optimizing one risk factor may also improve other related risk factors (e.g., reducing cigarette smoking may improve behavior related to diet, exercise and alcohol).

We need strong public health programs at all governmental levels to act as a behavioral immune system (Pernick 2021b) to reduce cancer deaths. Government, as well as nonprofits, the business community and others, should promote programs and policies, such as the American Code Against Cancer, that advance a culture of being healthy and make one's own health a priority. In addition, to the extent possible, all institutions should develop and implement their own cancer action plans.

We should also optimize access to medical care that reduces cancer deaths. This includes providing care to all patient populations and reducing disparities based on race or ethnicity, region of residence and socioeconomic status (Ma 2019, Michigan Cancer Plan 2021-2030 (PDF)).

9. We should develop better screening programs for cancers with high mortality.
This includes earlier detection of lung, pancreatic and liver cancers, aggressive colorectal, breast and prostate cancers and life threatening second cancers (Zaorsky 2017). We should study whether screening for the chronic inflammation associated with many cancers is useful and if so, how best to do it (Pernick 2021a).

To substantially reduce cancer deaths requires that we regularly update our strategy incorporating all of these proposed policies. Let's get to work!
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