Theories on the origin of Cancer

There are many theories on the origin of cancer. Some, such as the Somatic Theory of cancer have been around for a long time while others such as the Cell Suppression Theory are recent contributions to our understanding.

This page looks at the current theories of cancer, including the treatment proposed to best address cancer in line with some of these theories.

“Knowing the origin of cancer would have profound implications on our current conception and perception of cancer. It would affect our conduct in cancer research and our delivery of cancer care.”
Shi-Ming Tu, MD Anderson Cancer Center

Twenty-four Theories on Cancer Origin

Cancer usually originates when a vulnerable cell exists inside a vulnerable tissue environment.

That vulnerability may come from mutations, epigenetic instability, stem-cell dysregulation, mitochondrial dysfunction, chronic inflammation, infection, hormonal stimulation, immune escape, environmental exposures, ageing, or tissue disorganization. In real cancers, these are rarely isolated. They reinforce each other.

For example:

1. A carcinogen damages DNA.
2. Chronic inflammation promotes survival of damaged cells.
3. Epigenetic changes loosen differentiation control.
4. The microenvironment becomes fibrotic, hypoxic, and immune-suppressive.
5. Stem-like subclones emerge.
6. Metabolic rewiring supports survival.
7. Immune escape allows expansion.
8. Clonal evolution produces invasion, metastasis, and resistance.

So the best answer is not “cancer is genetic” or “cancer is metabolic” or “cancer is environmental.” Those are partial truths. Cancer is best understood as a systems failure of multicellular control, where genetic, metabolic, immune, tissue, microbial, hormonal, and environmental pressures converge.

1. Somatic Mutation Theory (SMT)

The somatic mutation theory has been the prevailing paradigm in cancer research for the last 50 years.

This article says: In a nutshell, the somatic mutation theory (SMT) of cancer is that a change in the DNA of a somatic cell alters its characteristics so that it undergoes clonal expansion. Cells within this population acquire further mutations so that eventually a sub-clone emerges that is able to grow or metastasize sufficiently to cause death of the host.

Note: This theory is now being seriously questioned because of the poor success rate of the treatments based on it (chemo, radiation etc).
See:
Somatic Mutation Theory – Why it’s Wrong for Most Cancers
Paradoxical Behavior of Oncogenes Undermines the Somatic Mutation Theory

2. Tissue Organization Field Theory (TOFT)

In this article the authors state: The somatic mutation theory of carcinogenesis has been the dominant force driving cancer research during the 20th century…We propose the adoption of an alternative theory, the tissue organization field theory of carcinogenesis and neoplasia. Its basic premises are that (1) proliferation is the default state of all cells and (2) carcinogenesis and neoplasia are defects of tissue architecture. Carcinogens would act initially by disrupting the normal interactions that take place among cells…

3. Immunological Theory

This theory has been associated with three general steps the body constantly goes through: elimination, equilibrium and escape. The elimination step consists of the immune system surveying for all cancerous cells and destroying them. However, there are times when tumorous cells remain undetected while remaining dormant. This period is defined as equilibrium because there are cancerous cells in the body, but they are not doing any harm. The final step is escape in which the tumor gains dominance over the immune system and starts spreading (Lopez, et al., 2016). This implies that the immune system’s activity and ability to detect cancerous cells is important before the cancer gets out of hand. Source

4. Viral, Bacterial, and Parasitic Origin Theory

Sources:
National Library of Medicine
National Cancer Institute
PubMed
Study
Study
National Cancer Institute

5. Bacterial Theory

Bacteria and bacterial infections can act as potential carcinogens and tumor promoters. The production of bacterial toxins, enzymes, and oncogenic peptides can all significantly contribute to tumor development by promoting inflammation, interfering with cell cycle control, and disrupting cell signaling pathways. Other studies have also corroborated the fact that microbiota-mediated infection stimulates cancer cell proliferation by targeting host cell DNA, altering the immune system, and promoting epithelial-to-mesenchymal transition.

Helicobacter pylori infection is implicated in the etiology of gastric cancer, and persistent Chlamydia infections present a risk factor for the development of cervical carcinoma, especially in patients with the human papillomavirus (HPV) coinfection. Salmonella typhi infections are linked with gallbladder cancer, and Chlamydia pneumoniae infection is implicated in lung cancer, etc. Source

6. Mitochondrial Metabolic Theory

This article says:
According to the MMT, cancer arises from a gradual disruption of ATP synthesis through oxidative phosphorylation (OxPhos) leading to compensatory ATP synthesis through substrate level phosphorylation. It is defective OxPhos that ultimately causes most of the genomic changes in cancer…The disruption of OxPhos leads to the accumulation of reactive oxygen species (ROS), which are mutagenic and carcinogenic. The genomic instability and somatic mutations seen in most cancers arise as a consequence of the chronic production of ROS and acidification of the microenvironment.

Proposed Treatment Protocol: Ketogenic metabolic therapy (KMT)
Glucose and glutamine are the two major fermentable fuels for cancer cells. Glucose drives tumor growth through glycolysis in the cytoplasm, while glutamine drives tumor growth through glutaminolysis in the mitochondria. Restriction of fermentable fuels is therefore an effective therapeutic strategy for cancer management. Ketogenic metabolic therapy (KMT) lowers blood glucose while elevating blood ketone bodies, a “super fuel” for normal cells, but a nonfermentable fuel for cancer cells. The efficacy of KMT for cancer management can be enhanced when used together with glutamine-targeting drugs and procedures that further inhibit fermentation. Source

7. Mitochondrial-Stem Cell Connection

In a recently published study, a new concept was introduced the mitochondrial-stem cell connection (MSCC). This concept combines the cancer stem cell theory and the metabolic theory.

The mitochondrial–stem cell connection (MSCC) proposes that tumorigenesis may result from an alteration of the mitochondria, specifically a chronic oxidative phosphorylation (OxPhos) insufficiency in stem cells, which forms cancer stem cells (CSCs) and leads to malignancy

Source: Mitochondrial–Stem Cell Connection: Providing Additional Explanations for Understanding Cancer Martinez et al.

Proposed Treatment Protocol
See Mitochondrial-Stem Cell Connection: Treatment Protocol page

8. Cell Suppression Theory

Proposed by Mark Lintern
“Challenging the mainstream narrative, I have amassed a formidable body of evidence that indicates cancer is one disease that is triggered and mediated by a number of opportunistic intracellular pathogens. Taking advantage of chronic inflammation to sustain an infection, leads to the symptoms that we refer to collectively as ‘cancer.”

Proposed Treatment Protocol (35 key considerations).
See Cell Suppression Theory page

9. Clonal Evolution Theory

According to this study, the classical model of clonal evolution, derived from Nowell envisages, sequential acquisition of mutations with concomitant, successive sub-clonal dominance or ‘selective sweeps’. Histopathological, time-ordered correlates of disease progression, i.e. adenoma, carcinoma, metastases, encourage this view. At all stages of this evolution, however, individual cells and their progeny (i.e., subclones) are vying for space and other limiting resources. Multiplexed, single cell mutational analysis (ideally in serial samples) is the appropriate way to interrogate clonal architecture. There are only a few examples of this to date though they do provide evidence for complex patterns of sub-clonal segregation of mutations, consistent with Nowell’s model. Collectively, a large body of data from tissue section, small biopsy and the more recent single cell analyses testifies to the fact that the evolutionary trajectories that emerge are complex and branching, exactly as envisioned by Nowell, providing a striking parallel with Charles Darwin’s iconic evolutionary speciation tree. 

An alternative therapeutic strategy directs attention away from the cancer cells and towards their micro-environmental habitats. There are many opportunities here for so-called ‘ecological’ therapy, directed at changing the essential habitat and dependencies of cancer cells. Anti-angiogenesis is a prime example of this tactic and may provide a potent restraint on CSCs. Other examples include interference with bone remodelling with bisphosphonates in prostate cancer, aromatase inhibitors in breast cancer, exploiting hypoxia, inhibitors of inflammation or tumour infiltrating macrophages and blockage of CSC interactions with essential stromal or niche components.

A further alternative is to seek to control cancer, rather than eradicate it, turning cancer into a chronic disease. Since the speed of evolution is proportional to the fitness differential between cells, cytotoxic drugs are predicted to rapidly select for resistance⁵. They likely cause competitive release, by removing all the competitors of the resistant cells. In contrast, cytostatic drugs should delay progression and mortality longer than cytotoxic drugs, because sensitive competitor cells remain to occupy space and consume resources that would otherwise benefit the resistant clones. In addition, by suppressing cell division, cytostatic drugs also suppress the opportunities for new mutations. Intriguingly, Gate by and colleagues have recently shown that by treating an aggressive ovarian cancer (OVCAR-3) xenograft tumour to maintain a stable size, rather than eradicate it, they were able to keep the host mice alive indefinitely. Moreover, the dose of carboplatin necessary to keep the tumour in check declined over time. We should be asking what phenotypes can we select for that would make neoplasm less deadly and more clinically manageable?

10. Cancer Stem Cell Theory

This study says a stem cell theory of cancer argues for a hierarchical model in which only certain cells in a stem cell hierarchy may develop into distinct tumor subtypes. Classic experiments using mouse strain 129 showed that embryonal carcinoma cells (rather than teratoma cells) isolated from teratocarcinomas underwent self-renewal and differentiation into a wide variety of cell types. Those experiments laid the groundwork for embryonic stem cell (ESC) research. Importantly, they established that embryonal carcinoma cells constitute the abnormal malignant counterparts of ESCs and revealed an uncannily close relationship between cancer cells and stem cells.

Ways to target stem cells: Cancer Stem Cells and Senescent Cancer Cells

11. Chronic Inflammation Theory

This study says: Here, we propose a dynamic association of the key features of tumour development, including chronic inflammation, deaminase dysfunctions, intratumor genetic heterogeneity, and cancer phenotypic plasticity. Importantly, the idea presented in this study does not contradict any of the previously established postulates and experimental observations, but it may present a more accurate point of view with interesting clinical implications. In summary, the model proposed here combines previously established tumour development theories: primary tumours may emerge in the background of chronic inflammation and may grow at the earlier stages according to the stochastic hypothesis. In an advanced stage of tumour progression, the CSC population coming from well-differentiated cancer cells may appear at the edges of the solid tumour mass according to the dynamic model. Finally, CSCs may migrate to distant organs where they may promote metastatic growth according to the hierarchic theory.

12. Epigenetic Theory

Study: According to its most popular definition, epigenetics describes the acquisition of measurable and stably heritable phenotypic traits that do not depend on changes in the DNA sequence itself. Epigenetic control, mediated by the integrative network of histone and DNA covalent modifications, as well as noncoding RNAs, coordinates the cell phenotype and allows genetically identical cells to achieve diverse phenotypic characteristics by modulating the accessibility of different regions of the genome through differential packaging and decoration of the chromatin. However, although the contribution of epigenetic mechanisms is relatively well characterized during embryogenesis, the precise involvement of those mechanisms in adult stem cell homeostasis has only recently started to be clarified . Of note, much of our current knowledge on the dynamics and function of stem cells actually arises from the study of mechanisms involved in the homeostatic rupture associated with cancer initiation and development. After a long period of mostly being perceived as the simple phenotypic result of sequential mutations in oncogenes and tumor suppressor genes, cancer is nowadays widely recognized to represent the outcome of the combinatorial effect of genetic and epigenetic alterations. Alterations in the epigenetic mechanisms are therefore now considered as relevant as genetic mutations in explaining the properties that define cancer cells at the various stages of the disease. It comes hereafter as no surprise that the outstanding accomplishments made during the last few decades in the identification of the genetic changes involved in cancer development have been accompanied by comparable advances in the characterization of the epigenetic control of malignancies. This characterization includes (but is not limited to) the role of widespread epigenomic changes, such as the global alteration of DNA methylation profiles, nuclear architecture and chromatin compaction. For multiple reasons, including the relative ease to recover the substrate from different types of biological samples, DNA methylation has so far represented the most well studied epigenetic modification in cancer.

13. Developmental / Reprogramming Theory

The developmental theory sees cancer as a disease in which adult cells reactivate embryonic, fetal, or wound-healing programmes. Some authors describe cancer as a reprogramming-like disease, where differentiation becomes unstable and cells revert toward a more plastic, primitive state.
This theory overlaps strongly with cancer stem cells, epithelial–mesenchymal transition, wound-healing biology, and embryonic signalling pathways such as Wnt, Hedgehog, Notch, TGF-β, and Hippo/YAP. See this study.

14. Atavistic Theory

This study says: Here we critically review one such hypothesis, named “atavism,” which puts forward the idea that cancer results from the re-expression of normally repressed genes forming a program, or toolbox, inherited from unicellular or simple multicellular ancestors. This hypothesis places cancer in an interesting evolutionary perspective that has not been widely explored and deserves attention. Thinking about cancer within an evolutionary framework, especially the major transitions to multicellularity, offers particularly promising perspectives.

15. Aneuploidy / Chromosomal Imbalance Theory

The loss or gain of one or more chromosomes is known as aneuploidy.

The aneuploidy theory argues that cancer originates from large-scale chromosomal abnormalities rather than individual gene mutations alone.

Aneuploid cells have abnormal chromosome numbers, leading to widespread gene dosage imbalance, proteotoxic stress, altered metabolism, genomic instability, and malignant adaptation.

This theory has appeal because many advanced cancers are profoundly aneuploid, and chromosomal chaos often correlates with aggressiveness.
See Study

16. Field Cancerisation Theory

The field cancerisation theory proposes that large areas of tissue become preconditioned for cancer because of shared exposure to carcinogens, inflammation, infection, ageing, or epigenetic damage.

Instead of one isolated bad cell, the tissue field becomes abnormal. Multiple independent cancers or precancerous lesions may then arise within the same damaged field.

17. Immune Surveillance Failure Theory

The immune surveillance theory proposes that abnormal cells arise frequently, but most are detected and eliminated by the immune system. Cancer emerges when abnormal clones escape immune detection or create an immunosuppressive microenvironment.

This theory underpins immune checkpoint inhibitors, cancer vaccines, adoptive T-cell therapy, and interest in immune-supportive lifestyle or microbiome interventions.

18. Microbiome Dysbiosis Theory

The microbiome theory argues that altered microbial ecosystems can contribute to cancer initiation and progression by influencing inflammation, immune tone, metabolism, bile acids, toxins, oestrogen recycling, epithelial barrier integrity, and treatment response.

This is not yet a universal origin theory, but it is increasingly important in colorectal, gastric, liver, pancreatic, breast, and immunotherapy-response research.

19. Endocrine / Hormonal Theory

The hormonal theory proposes that prolonged or dysregulated hormone signalling can drive cancer initiation or promotion in hormone-sensitive tissues.

Hormones may not directly “mutate” cells in the classic sense, but they can increase proliferation, reduce apoptosis, alter metabolism, and create a permissive environment in which mutations or epigenetic errors become more consequential.
This theory supports attention to obesity, insulin resistance, reproductive history, endocrine disruptors, hormone replacement, androgen/oestrogen signalling, and metabolic health.

20. Environmental Carcinogenesis Theory

The environmental theory argues that cancer originates from external exposures that damage DNA, disrupt endocrine signalling, alter immunity, or produce chronic tissue injury.

This model integrates easily with somatic mutation theory, inflammation theory, epigenetic theory, and tissue-field theory.

21. Ageing / Senescence Theory

The ageing theory sees cancer as partly a consequence of ageing tissues.

With age, cells accumulate mutations, epigenetic drift, mitochondrial dysfunction, telomere attrition, immune decline, senescent-cell burden, chronic low-grade inflammation, and stem-cell exhaustion. Age is not merely a time variable. It changes the biological terrain in which cancer can emerge.

22. Bioelectric / Biophysical Theory

A more unconventional but increasingly discussed theory is that cancer can arise from disrupted bioelectric signalling, mechanical forces, tissue polarity, and cellular communication.

Cells do not only communicate chemically; they also use voltage gradients, ion channels, membrane potential, mechanical tension, and spatial patterning cues. Disruption of these systems may contribute to loss of tissue organization and malignant behaviour.

23. Trauma / Wound-Healing Theory

The wound-healing theory proposes that cancer resembles a wound that does not properly heal. Normal wound healing involves inflammation, cell proliferation, angiogenesis, immune modulation, matrix remodelling, and temporary suppression of normal tissue architecture. Cancer may emerge when this programme becomes chronic or dysregulated.

This model is associated with the phrase: “tumours are wounds that do not heal.”

This theory is highly relevant to fibrosis, chronic injury, obesity-related inflammation, surgical wound biology, and tumour microenvironment research.

This Non-thematic Review says:
 Our proposed hypothesis is that cancer is a natural wound healing-related process, which includes oncogene activations, cytokine secretions, stem cell recruitment differentiation, and tissue remodeling. Wounds activate oncogenes of some cells and the latter secrete cytokines to recruit stem cells to heal the wounds. However, if the cause of the wound or if the wound persists, such as under the persistent UV and carcinogen exposures, the continuous wound healing process will lead to a clinical cancer mass. There is no system in nature to stop or reverse the wound healing process in the middle stage when the wound exists. The outcome of the cancer mechanism is either healing the wound or exhausting the whole system (death). The logic of this cancer mechanism is consistent with the rationales of the other physiological metabolisms in the body—for survival. This hypothesis helps to understand many cancer mysteries derived from the mutation theory, such as why cancer only exists in a small proportion of multicellular organisms, although they are all under potential mutation risks during DNA replications. The hypothesis can be used to interpret and guide cancer prevention, recurrence, metastasis, in vitro and in vivo studies, and personalized treatments.

24. Psychological Stress Theory

This Study Review says: The results of 165 studies indicate that stress-related psychosocial factors are associated with higher cancer incidence in initially healthy populations; in addition, poorer survival in patients with diagnosed cancer was noted in 330 studies, and higher cancer mortality was seen in 53 studies. Subgroup meta-analyses demonstrate that stressful life experiences are related to poorer cancer survival and higher mortality but not to an increased incidence. Stress-prone personality or unfavorable coping styles and negative emotional responses or poor quality of life were related to higher cancer incidence, poorer cancer survival and higher cancer mortality. Site-specific analyses indicate that psychosocial factors are associated with a higher incidence of lung cancer and poorer survival in patients with breast, lung, head and neck, hepatobiliary, and lymphoid or hematopoietic cancers. These analyses suggest that stress-related psychosocial factors have an adverse effect on cancer incidence and survival, although there is evidence of publication bias and results should be interpreted with caution.

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Last updated January 2026