Critical Times

section 15 PSiC by P Henry

Cancers are multifactorial illnesses. Genetic predispositions, human activities, endogenous & exogenous phenomena can all trigger or increase cancer. They cause the most life-years disability, requiring a multidisciplinary approach.

There is much more research required and hopefully these notes can encourage such work.

Psychosocial

Exploring psychosocial interventions requires both qualitative and quantitative skills. What is known about cancer stimulates stresses and anxieties, the many facets of what the patient apprehends and the professionals imply. Which techniques would be the most helpful in addressing the accompanying foreboding feelings? Stresses and anxieties arise with what is known about cancer: the multilayers of what is implied and apprehended. There are also concerns about the unknown. These can threaten. They involve isolation, rejection, impairment, suffering, confusion, death – these are all still common, unmitigated experiential realities.

Many areas require further research, to increase its efficiency and dispel cursory rejection of Psychooncology practices, include: 1) Detail those techniques that are most useful for which cancer under what circumstances. 2) Address how distress and foreboding accompany cancer’s onset and its symptoms. 3) Show its role in maintenance and outcomes.  4) Detail how an individual’s stresses and anxieties arise with what is known about cancer, what is implied and experienced, what are threats of the unknown. (Can cancer be without stress?) 5) Connect individuals and significant others, with suffering, impairment, rejection, confusion, death threats of cancer. These are often shared. 6) Understand stressors and individual defences, related to environment and developmental issues. 7) Examine the effects of all alternative interventions. 8) Detail applications of PNI. 8) Directly connect psychosocial therapies to biochemical treatments.

Biochemistry and Medical

Within these sciences, it would be useful to have elaboration on the many studies of the HPA axis (hypothalamic-pituitary-adrenocortical) functions and dysfunctions relating to cancers[1]. How the HPA releases hormones, secretes glucocorticoids, acts on many organs, interacts with various biofeedback biochemical systems. How these connect to increasing or reducing stressors and progress cancer. Showing how to create specific interventions while the HPA attempts (along with the autonomic, central & peripheral nervous systems) to accommodate those perceptions and activities of threat through fight, flight or freeze responses and return the human bio-system to a homeostasis contrasting a strained allostasis.  

Allostatic load affects cancer[2]. This relates how homeostatic changes lead to allostatic attempts to cope. This often leads to overload which affects the endocrine, HPA, and immune systems, influencing oncogenesis[3]. There is a reciprocal relationship between oncogenesis and allostatic load[4].

This may help understand the immune system’s difficulties dealing with cancer.

Cancer promotion, progression, tumorigenesis and reoccurrences can also be connected to epigenetic changes[5]. These “epigenetic changes are inherited but repairable genetic DNA modifications that affect gene expression regardless of the underlying sequence” [6].  Epigenetics reveal heritable and modifiable gene expression. This suggests that a cancer gene in the DNA can become activated. Additionally, telomere status regulates cancer cell growth by participating directly in cellular metabolism, signal transduction, and the regulation of gene expression in ways that are critical for tumorigenesis[7].

Abnormal epigenetic changes can incorrectly activate oncogenes, creating cancer abnormalities. Epigenetics can have an effect on “regulatory pathways, signalling, DNA methylation, microRNAs modulation of serotonin and dopamine….”[8].  It can be modified through developmental and environmental activities[9].

Telomeres, at the end of chromosomes, are specific DNA structures. With telomerase they help chromosome stability, homeostasis and maintenance.[10] A connection between telomeres’ length and risk of cancer is identified[11]. Telomere length has been shown to be affected by stress, modified by psychological therapy, and an indicator of vulnerability to cancer[12]. The length of the telomeres is significant to cancer outcome[13]. It can affect pathways, genome instability and induce cancer changes[14]. 

This brief summary shows that the complexity of cancer requires interdisciplinary collaboration and cooperation, to understand the interplay between their varied parameters and findings.

[1] Hypothalamic–Pituitary–Adrenal Axis Dysfunction in People With Cancer: A Systematic Review. (2023) N G Kanter et al. Cancer Medicine 13(22).

[2] Allostatic load and cancer risk, progression, and mortality in epidemiologic studies. (Jun25)

N Ishibe et al. Am J of Epidemiology 194( 6). Cell competition in development, homeostasis and cancer. (29Sept22) S M van Neerven et al. Mol Cell Bio 24.  Cell competition in development, homeostasis and cancer. (29Sept22) S M van Neerven et al. Mol Cell Bio 24.  Cancer as a Homeostatic Challenge: The Role of the Hypothalamus. (21Set21). N Francis et al. Trends Neurosci. 2021 Sep 21;44(11). …Integrating homeostasis, allostasis and stress. (26Sept09) B S McEwen et al. Horm Behav. 57(2).

[3] Retrospective operationalization of allostatic load in patients with cancer…. (Sep24) E N McQuitty et al. Psychoneuroendocrinology 167.  How cancer hijacks the body’s homeostasis through the neuroendocrine system. (Apr23) M.Radomir et al. Trends in Neurosciences 46(4).  Allostatic Load in Cancer: A Systematic Review and Mini Meta-Analysis. (3Nov23) A Mathew et al. Biol Res Nurs.;23(3). 

[4]   …Integrating homeostasis, allostasis and stress. (26Sept09) B S McEwen et al. Horm Behav. 57(2).

[5]Mechanisms and technologies in cancer epigenetics. (1Jan25) Zaki A Sherif et al. Front Oncol.14.

Cancer epigenetics: from laboratory studies and clinical trials to precision medicine. (2024) Xinyang Yu, et al. Cell Death Discovery 10(28).

[6] Allostatic load and cancer risk, progression, and mortality in epidemiologic studies. (2025) N Ishibe et al.  m J of Epidemiology, 194(6).  Cancer as a Homeostatic Challenge: The Role of the Hypothalamus. (21Set21) N Francis et al. Trends Neurosci. 2021 Sep 21;44(11).   The role of epigenetics in cancer: From pathways to the clinic. (24Sept25) A A Almalki. J Family Med Prim Care 14(8).  Epigenetic Regulation of Development, Cellular Differentiation, and Disease Progression/Protection in Adults. (12Jun22) R J Ryznar et al. Cells11(12).

[7]Early Life Stress and the Onset of Obesity: Proof of MicroRNAs’ Involvement Through Modulation of Serotonin and Dopamine Systems’ Homeostasis. (28Jul2008)G A Tavares et al. Front Physiol.11.

[8] The role of epigenetics in cancer: From pathways to the clinic. (24Sept25) A A Almalki et al. J Family Med Prim Care.14(8).   [9] How Diet Influences Gene Expression Through Epigenetic Mechanisms. (2026) V Kumar Malesu et al. News Med Lifesciences.  Restoring Epigenetic Reprogramming with Diet and Exercise to Improve Health-Related Metabolic Diseases. (2023) M J