Destabilization of Abnormal Methylation Enzymes: Nature’s Way to Eradicate Cancer Stem Cells

Liau, Ming C.; Kim, Jai Hyun; Fruehauf, John P.

doi:10.33552/ojcam.2019.02.000546

Cited by 6 publications

(13 citation statements)

References 72 publications

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“…The close relationship between cancer and wound healing was noticed by MacCarthy-Morrough and Martin [4]. We provided the most important details on this subject that included abnormal MEs to block differentiation [5][6][7]; chemo-surveillance as a natural mechanism to ensure perfection of wound healing to avoid cancer [8][9][10][11]; DIs and DHIs as the wound healing metabolites and also as the active players of chemo-Surveillance [9][10][11]; hypomethylation of nucleic acids as the most critical mechanism to achieve terminal differentiation of cells with abnormal MEs [12]; the mechanism of wound healing [13][14][15]; and the evolution of CSCs from PSCs [16]. Our studies clearly established that cancer arose as a consequence of wound not healing properly due to the collapse of chemo-surveillance, thus allowing PSCs to evolve into CSCs, and then to progress to faster growing CCs through activation of oncogenes and/ or inactivation of suppressor genes.…”

Section: Commentaries and Discussionmentioning

confidence: 99%

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Winning Formulas to Fulfill Cancer Moonshot

Liau¹,

Fruehauf²

2022

Int J Res Oncol

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The objective of this study was to develop winning formulas to fulfill cancer moonshot declared by President Biden on Sept. 12, 2022, the 60th anniversary of the moonshot speech of President Kennedy. The intention of President Biden was to use the spirit of successful moonshot project to salvage the failure of war on cancer project declared by President Nixon in 1971 [1]. Cancer therapies based on killing of cancer cells were the choice of cancer establishments in the past. The choice of killing cancer cells is understandable because the perpetual replication of cancer cells constitutes the most outstanding feature of cancer. Cancer is contributed by multiple factors. Factors other than replication of cancer cells also play essential roles on the development of cancer. Cancer arises as a consequence of wound not healing properly due to the collapse of chemo-surveillance, thus allowing Progenitor Stem Cells (PSCs) to evolve into Cancer Stem Cells (CSCs), and then to progress to faster growing Cancer Cells (CCs) through activation of oncogenes and/or inactivation suppressor genes. Cell killing creates more wounds to aggravate the already bad situation on the functionality of chemo-surveillance, which is an important mechanism to suppress the build-up of cells with abnormal Methylation Enzymes (MEs) that include PSCs, CSCs, and CCs. PSCs and their immediate derivatives CSCs are protected by drug resistant and anti-apoptosis mechanisms. Cytotoxic agents can wipe out CCs but cannot affect CSCs. The damage to chemo-surveillance contributed by cell killing agents allows CSCs to become dominant cells to cause he failure of cancer therapy, thus losing the war on cancer. Cell Differentiation Agent (CDA) formulations are the preparations consisting of Differentiation Inducers (DIs) and Differentiation Helper Inducers (DHIs), plus phenylacetylglutamine as an anti-cachexia agent. Such preparations are perfect cancer drugs to take out both CCs and CSCs by the induction of terminal differentiation through destabilization of abnormal MEs, and to restore the functionality of chemo-surveillance. Cancer therapies mediated by CDA formulations are the nature’s choice to combat cancer that can fulfill the goal of President Biden’s cancer moonshot. CDA formulations, however, cannot make the tumor to disappear, which can be easily accomplished by therapies based on cell killing. President Biden’s goal is very modest, requiring reduction of cancer mortality 50% in 25 years. That goal can be easily accomplished by winning formulas that include CDA formulations and therapies to eliminate or to kill CCs. We offer the following winning formulas: 1. Therapy with CDA-CSC, a preparation made up by an approved DI and an approved DHI, to eradicate CSCs and CCs by the induction of terminal differentiation and to restore the functionality of chemo-surveillance, followed by the surgical removal of the residual tumor. 2. Surgical removal of the primary tumor, followed by the administration of CDA-CSC to prevent recurrence and metastasis, and to restore the functionality of chemo-surveillance. 3. Radiotherapy, immunotherapy, or chemotherapy to kill CCs, followed by the administration of CDA-CSC to eradicate CSCs and to restore the functionality of chemo-surveillance.

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Section: Commentaries and Discussionmentioning

confidence: 99%

“…Therefore, a moderately active DHI can have remarkable therapeutic effect to cure untreatable malignant brain tumors. The eradication of CSCs is essential for the success of cancer therapy [16,18,[37][38][39][40]. We are in a unique position to have the ability to eradicate CSCs.…”

Section: Winning Formulas To Fulfill Cancer Moonshotmentioning

confidence: 99%

Winning Formulas to Fulfill Cancer Moonshot

Liau¹,

Fruehauf²

2022

Int J Res Oncol

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“…So, destabilization of MEs is a critical mechanism to achieve wound healing and elimination of CSCs. Apparently, destabilization of abnormal MEs is a better choice than nucleoside analogs [54,55]. MDS is a good model for the test of right cancer drugs.…”

Section: Cscs At the Center Of Cancer Problemsmentioning

confidence: 99%

CDA Formulations to Fulfill Cancer Moonshot and to Win the War on Cancer

Liau¹,

Craig²,

Baker³

2023

Int J Res Oncol

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The objective of this study is to call for approval of cell differentiation agent (CDA) formulations as the right cancer drugs to save cancer patients. Moonshot was a presidential project to set a classic record of success attributable to the right approach and war on cancer was another presidential project to set a classic record of failure attributable to the wrong approach. Cancer moonshot was brought up by President Biden to urge health profession to rely on right approaches to save cancer patients. Perpetual replication of cancer cells (CCs) is the most outstanding feature of cancer. Naturally, killing of replicating CCs becomes the top choice of cancer establishments to combat cancer. Killing of CCs is actually a wrong approach of cancer therapy, because cancer is caused by wound unhealing due to the collapse of chemo-surveillance, which is a natural mechanism to ensure perfection of wound healing. Killing of CCs by cytotoxic agents promotes cancer stem cells (CSCs) to proliferate in order to repair the damages created by cytotoxic agents, eventually pushing CSCs to reach a high proportion to become unresponsive to further treatments. Killing of CCs is a wrong approach that causes the failure of cancer solution. To save cancer patients, we have to drastically change past practices. Apparently, wound healing process is the right approach of cancer therapy. Induction of terminal differentiation of PSCs is the most critical mechanism of wound healing, which is achieved by differentiation inducers (DIs) and differentiation helper inducers (DHIs). CDA is a collective term of the preparations consisting of different proportions of DIs and DHIs. Therefore, CDA formulations are the best solution of cancer to fulfill cancer moonshot and to win the war on cancer. CDA formulations display the features as pro-wound healing that can eliminate both CSCs and CCs by inducing these cells to undergo terminal differentiation, and to restore the functionality of chemo-surveillance, which is the creation of the nature to prevent the buildup of cells with abnormal MEs. A perfect cancer drug must have the ability to eliminate both CSCs and CCs, and to restore the functionality of chemo-surveillance. CDA formulations fit the description as perfect cancer drugs to fulfill cancer moonshot and to win the war on cancer.

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“…The evolution of CSCs from PSCs is very simple. A single hit to silence TET-1 enzyme can convert PSCs to become CSCs, which is a task easily accomplished by PSCs equipped with abnormally active MEs [24]. Chemo-surveillance is a very important mechanism to prevent that from happening.…”

Section: Chemo-surveillancementioning

confidence: 99%

“…The progress of CSCs to faster growing CCs is just a matter of time. These are exactly the sequence of events taking place on the evolution of CSCs from bone marrow PSCs to become myelodysplastic syndrome (MDS), and then progress to become acute myeloid leukemia [1,24]. The best solution of cancer is to follow the course of successful wound healing.…”

Section: Cancer As Failed Wound Healingmentioning

confidence: 99%

No Scar as an Indication of Perfect Wound Healing, Ugly Scar as Imperfect Wound Healing and Cancer as Failed Wound Healing

Liau¹,

Craig²

2022

JCTI

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Wound healing and cancer evolution are closely related to involve progenitor Stem Cells (PSCs) as the critical common elements. Wound healing requires the proliferation and the Terminal Differentiation (TD) of PSCs. Wound triggers biological and immunological responses. The biological response involves the release of Arachidonic acId (AA) from membrane bound phosphatidylinositol for the synthesis of prostaglandins (PGs) which are active differentiation inducers (DIs) good for wound healing. Immunological response prompts the production of Tumor Necrosis Factor (TNF), which is also named cachectin after its effect to cause cachexia symptom. Cachexia symptom is bad for wound healing, because of excessive urinary excretion of low molecular weight metabolites resulting in the loss of wound healing metabolites. The proliferation of PSCs is promoted by PGs and the TD of PSCs is accomplished by metabolites involved in chemo-surveillance. Thus, the functionality of chemo-surveillance plays an important role to dictate the success of wound healing. If the functionality is perfect as healthy people, healing of wound with no scar can always be expected. But if the functionality of chemo-surveillance has been damaged due to pathological conditions causing cachexia symptom, then healing of wound may be impaired to result in ugly scar, or even worse cancer. Ugly scar in visible surface is a medical concern, particularly with respect to cosmetic surgery. Cancer is a very fearful disease. The study of wound healing is helpful to heal wound with no scar and to search for a more appropriate strategy of cancer therapy. Data in support of this opinion article were produced by Ming C. Liau as a volunteer researcher during 2010 to 2020 in the laboratory of Professor John P Fruehauf at Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, CA,USA.

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Destabilization of Abnormal Methylation Enzymes: Nature’s Way to Eradicate Cancer Stem Cells

Abstract: Cancer therapy is dominated by cytotoxic agents that act via mechanisms that damage DNA and activate apoptotic pathways.While cytotoxic agents have been moderately effective to eliminate symptoms and to extend the life span of cancer patients, this

Cited by 6 publications

References 72 publications

Winning Formulas to Fulfill Cancer Moonshot

Winning Formulas to Fulfill Cancer Moonshot

CDA Formulations to Fulfill Cancer Moonshot and to Win the War on Cancer

No Scar as an Indication of Perfect Wound Healing, Ugly Scar as Imperfect Wound Healing and Cancer as Failed Wound Healing

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