Cancer Can Be Reversed in A Breeze, How? The Myth of Gene Mutation in Cancer Formation

The somatic mutation theory (SMT) of cancer formation has been the dominant force driving cancer research during the 20th century. In brief, it proposes that successive DNA or gene mutations in a single cell cause cancer (monoclonality). Its basic premises are that (1) cancer is a defect of the control of cell proliferation and (2) the default state of metazoan cells is quiescence (Sonnenschein C, 2000).

Is Cancer Reversible?

Cancer has been historically considered to be irreversible, because gene mutations are not known as reversible.

However, cancer cells in normal microenvironments have been shown to revert spontaneously to nonmalignant cells (Kenny PA et al, 2003). It is becoming increasingly clear that not all oncogenes are mutagens, and not all tumors are associated with specific mutations. Many of the mutations associated with cancer have also been found in healthy cells and that cells reverted from cancer status do not show any correction of mutated genes.

Studies showed that only 30–40% of cancer cells present genetic mutations, while mutations in genes highly correlated with tumors have been found in healthy cells. Furthermore, some tumors do not present mutations at all (Pensotti A et al, 2023).

These evidences tell us that it is possible to transform cancer cells from malignant to benign (Cho KH, 2017). This process from malignant to benign is known as “cancer reversion” or “tumor reversion”.

Microenvironment Can Alter Gene Expression

The first clinical evidence of spontaneous cancer regression came from teratocarcinoma. In 1907, the Swiss pathologist, Max Askanazy, observed the spontaneous reversion of an ovarian teratocarcinoma (Askanazy M 1907). This observation was confirmed in 1954 after Stevens and Little’s work on the 129 mice had led to a model of teratocarcinoma (Stevens L.C et al, 1954).

In 1961, Pierce GB et al's study demonstrated the pivotal role of the cell microenvironment in the differentiation of embryonal carcinoma cells to benign forms ( Pierce GB et all, 1961).

These results were instrumental in introducing the concept of “cancer reversion”, indicating the recovery of a normal phenotype by cancerous cells when exposed to a specific microenvironment (Pensotti A et al, 2023).

In 1974, Brinster confirmed Pierce’s hypothesis. He injected testicular teratocarcinoma cells from the 129/SvJ black agouti into murine blastocysts, and then implanted these blastocysts into albino female mice. This resulted in a healthy black-white hybrid offspring, suggesting that “the embryo environment can bring under control the autonomous proliferation of the teratocarcinoma cells” (Brinster RL, 1974).

Similar results were obtained by Mintz et al (1975). They had injected embryonal cancer cells into 280 different blastocysts that were further implanted into as many adoptive mother mice. Both analyses on the fetus and the offspring showed no signs of cancer cells. Even more interesting were the results of the analyses on the composition of hair, the type of circulating red and white blood cells, the protein composition of urine, and the characteristics of the kidneys, liver, and thymus.

From all of these results, Mintz et al concluded (Mintz et al, 1975):

“The capacity of embryonal carcinoma cells to form normally functioning adult tissues demonstrates that conversion to neoplasia did not involve structural changes in the genome, but rather a change in gene expression”.

Mintz et al's conclusions were supported by subsequent experiments which demonstrated the role of the embryonic microenvironment in controlling the proliferation of different cancer types such as Rous sarcoma, leukemia, neuroblastoma, melanoma, colon, and breast, to mention a few ((Pensotti A et al, 2023).

From the above experimental evidences, the following conclusions regarding DNA mutation & cancer formation can be drawn, namely (Pensotti A et al, 2023):

• Cancer cells display relevant plasticity, and their fate is not “irreversibly” determined.

• It is possible to inhibit the phenotypic expression of the malignant characteristics of cancer cells mostly through epigenetic processes.
• Gene mutations do not play a “causative” role as the somatic mutation theory (SMT) posits, albeit they can be associated throughout the process of cancer development.

Does Gene Mutation Cause Cancer?

For a long time, specific genes were believed to be associated with certain functions and characteristics expressed at a phenotypic level: “a gene–a function” had become a sort of axiom. Based on this dogma, the SMT has implicitly excluded the concept of tumor reversion: if the malignant cell characteristics are the result of genetic mutations, then it is impossible to eliminate them without first correcting these coding errors (Huang S, 2021).

As mentioned earlier, a plethora of anecdotal experiment observations show that not all oncogenes are mutagens, and not all tumors are associated with specific mutations.

Unexpectedly, cancer can develop even in the absence of specific mutated genes. For example, it has been observed that some oncogenes such as H-ras, N-ras, and K-ras are not clonal in the prostate, the colon and in melanomas. Mutations such as Her and EGFR, observed in tumors of the bladder and the breast, as well as in gliomas, are also non-clonal (Pensotti A et al, 2023).

Gene Mutation & Cancer: Chicken or Egg, Which Came First?

Surprisingly, certain mutations deemed to exert a causative role in malignant tumors are also detected in normal cells, while certain mutations affecting oncogenes and tumor suppressor genes often occur only in an advanced stage of cancer progression.

In some cases, as in the case of EGFR changes, these mutations occur only in a limited number of tumor cells. The same was observed for the oncogenes c-fos and c-erb B-3, which, paradoxically, turned out to be more frequent in healthy tissue cells than in colon cancer cells (Pensotti A et al. 2023).

Studies also show that only 30–40% of cancer cells present genetic mutations, while mutations in genes highly correlated with tumors have been found in healthy cells. Finally, some tumors do not present mutations at all .

These observations allow the scientific community to hypothesize that alterations in the “gatekeeper” and “caretaker” genes are not sufficient to initiate a tumor, and that perhaps the very hypothesis that cancer is the result of genetic mutations may be wrong (Prehn RT, 1994; 2005).

Search For Target-Drugs: A Futile Attempt

Cancer heterogeneity represents another critical issue: a tumor mass is composed of a heterogeneous population of cancer cells that, contrary to what was originally hypothesized by the monoclonal cancer origin model, show a different gene expression pattern as well as several relevant differences in phenotypic and behavioral traits (Pensotti A et al, 2023).

These targets, even when they are identified in a large fraction of the cancer cell population, could be numerous and constantly evolving, making it difficult to reach a definitive target-based solution for the treatment of cancer.

Generally, most of the anticancer drugs have not been able to make substantial contributions to the treatment of cancer patients, except disappointing results and the enormous imbalance between costs and benefits.

The best achievements performed along this path are actually limited to a six-month extension of the life expectancy of patients, with an average of around four months. In addition, many of these therapies fail to avoid relapses, which in most cases recur with greater malignancy than the primary tumor.

No Clinical Approach Available Yet to Reverse Cancer

During the last 40 years, the survival rate of patients suffering from different kinds of cancer has increased up to 20%. However, such achievement was mostly due to the early diagnosis and surgical and radiation-based therapies with too much adverse effects (Pensotti A et al, 2023) .

For solid cancers, no medical treatments such as target-based drugs available yet which could provide any clinically important benefits for cancer regression (Lichtenberg Fr, 2010; Hanahan D, 2014).

The Role of the Microenvironment

The initial concept of the microenvironment was developed in the seed and soil theory by Paget at the end of the 19th century. Nowadays, the cellular microenvironment means the environment surrounding the cell—a complex system composed of the extracellular matrix, capillaries, stroma cells, active substances (such as cytokines and hormones) and many other diffusible molecular factors (Pensotti A et al, 2023).

The cells, together with the tumor microenvironment, represent an integrated, dynamic system whose state is determined by the interactions of all of its components. When separated from their neighbors, cells lose most of their functional and structural attributes. A sort of causality reverberates from higher to lower levels: macromolecules, metabolites, genes, and proteins are all intimately linked to each other. They form an integrated system that changes according to the stimuli coming from the higher levels.

Evolutionary processes rarely act on single cells or distinct species. Rather, they affect complex multi-scale systems and the non-linear way that components interconnect.

Cells lose many of their differentiated functional characteristics when isolated and placed in a culture medium. This shows that cellular specialization depends on the context, i.e., the morphogenetic field. The morphogenetic field binds cells to a specific dynamic adaptation to external stimuli, such as shear or traction forces, compression, hydrostatic pressure, and even electromagnetism.

Cellular response occurs through cytoskeletal changes in shape and behavior. These modifications can, in turn, exert an influence on both their microenvironment (mechano-reciprocity) and gene expression in a self-regulating mechanism that guarantees the cell’s homeostasis.

The cellular microenvironment and its morphogenetic field can play a decisive role in the development or regression of cancer (Pensotti A et al, 2023).

What Is Cancer?

Each cell expresses only some genes of the entire DNA. For this reason, different cell types are distinguished at the histological level: hepatocyte, neuron, mesenchymal stem cell, etc (Pensotti A et al, 2023) .

During their life cycle, cells can change their behavior and phenotypic expression in reaction to external stimuli: the wound healing processes in which involved cells acquire a behavior that is very similar to that of cancer for a defined period are an emblematic case.

Tumor reversion represents a case of modification in phenotypic expression: the same genes, even if mutated, change the way they express and, consequently, the features and behavior of the cell.

Genes are not independent entities but belong to complex networks known as “gene regulatory networks”. Here, genes influence and bind to each other, further limiting the possible combinations of gene expression.

We can interpret cancer as a particular state of the cell that evolves over time within the “landscape model”. This transition from one state to another is fundamentally determined by two variables: the external signals and constraints, and the internal adaptive response of the cell (Pensotti A et al, 2023).

Biological Signals to Trigger Cancer Reversion

Accordingly, cancer should be interpreted as an epiphenomenon that emerges from the disintegration of the cell–microenvironment system.

The consequent therapeutic strategy should, therefore, no longer try to eliminate tumor cells. Rather, it should aim to induce a benign modification of the phenotype. Tumor reversion research points out that this phenotypic change can be induced through specific biological signals. These modify the microenvironment or, more generally, the morphogenetic field, and channel the cell toward new stable states (Pensotti A et al, 2023).

Are There Magic Bio-Signals for Triggering Cancer Reversion?

Yes. There are.

There are plentiful anecdotal observations in the last 2000 years which point to the possibility that cancer can be reversed in a breeze – through a neurological stimulation from the poking by tiny needles.

This needle poking technique comes from Neijing acupuncture – a healing art widely practiced 2000 years ago in China.

In my on coming posts, I will talk about how to stop cancer progression instantly and reverse it in 3 weeks, with basal cell carcinoma as an example, which is.a most common form of skin cancer. Interested readers, stay tuned.

References

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