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European Journal of Applied Sciences – Vol. 11, No. 1

Publication Date: February 25, 2023

DOI:10.14738/aivp.111.13904. Liau, M. C., Craig, C. L., & Baker, L. L. (2023). Wound Healing Process as the Most Appropriate Modality of Cancer Therapy.

European Journal of Applied Sciences, Vol - 11(1). 463-471.

Services for Science and Education – United Kingdom

Wound Healing Process as the Most Appropriate

Modality of Cancer Therapy

Ming C. Liau

CDA Therapeutics, Inc., 3308 Sky Run Court, Missouri City, TX 77459, USA

Christine L. Craig

CDA Therapeutics, Inc., 3308 Sky Run Court, Missouri City, TX 77459, USA

Linda L. Baker

CDA Therapeutics, Inc., 3308 Sky Run Court, Missouri City, TX 77459, USA

ABSTRACT

President Biden of USA declared cancer moonshot initiative on Sept. 12, 2022 to

urge the health profession to come up solutions to save 50% of cancer patients in

the following 25 years. Cancer therapies were dominated by strategy based on

killing of cancer cells in the past, which have been drilled through as a presidential

project, but failed to achieve the goal to win the war on cancer. Obviously, a drastic

change of strategy is necessary to fulfill moonshot of President Biden. Wound

healing requires the proliferation and the terminal differentiation of progenitor

stem cells (PSCs). Wound healing comes naturally, because the nature creates

chemo-surveillance to ensure perfection of wound healing. Healthy people are able

to maintain a steady level of wound heading metabolites active as differentiation

inducers (DIs) and differentiation helper inducers (DHIs) to promote terminal

differentiation of PSCs through destabilization of abnormal methylation enzymes

(MEs). The functionality of chemo-surveillance can be damaged under pathological

conditions triggering the production of tumor necrotic factor (TNF) to cause

cachexia symptoms. A manifestation of cachexia symptoms is the excessive urinary

excretion of wound healing metabolites to affect terminal differentiation of PSCs to

heal wound, allowing 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 of suppressor genes. Since cancer is caused by wound

unhealing. Thus, wound healing process offers the most appropriate modality of

cancer therapy. CDA-2 is a preparation of wound healing metabolites purified from

urine, which has superb therapeutic efficacy against myelodysplastic syndrome

(MDS). MDS is a disease caused by the build up of CSCs unable to undergo terminal

differentiation. Apparently, wound healing metabolites are the best medicine to

eradicate CSCs. For the therapy of cancer, we propose to add another set of DI + DHI

consisting of synthetic products to target CCs, since CCs are known to express high

levels of salvage enzymes to support their faster growth. CDA formulations

definitely can fulfill cancer moonshot. Perpetual replication of CCs is the most

outstanding feature of cancer. Naturally, killing of CCs becomes the choice of cancer

establishments to combat cancer in the past. This modality of cancer therapy has

been drilled through as a presidential project, but failed to achieve the goal to win

the war on cancer. The contribution to damage chemo-surveillance and the inability

to eradicate CSCs are responsible for the failure to save cancer patients. A

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Services for Science and Education – United Kingdom 464

European Journal of Applied Sciences (EJAS) Vol. 11, Issue 1, February-2023

combination therapy with CDA formulations can eliminate such deficit to fulfill

cancer moonshot.

INTRODUCTION

President Biden of USA declared cancer moonshot initiative on Sept. 12, 2022, the 60th

anniversary of the moonshot speech of President Kennedy [1]. This declaration was in essence

a protest of the failure to save cancer patients from the highest government official to the health

profession. The moonshot project was technologically a very difficult presidential project. So

far the USA was the only nation able to accomplish this difficult challenge. War on cancer was

another presidential project declared by President Nixon in 1971, which was not successful

despite technologically not as difficult as the moonshot project [2]. President Biden brought

two unrelated presidential projects together with an intention to urge the health profession to

learn from the successful moonshot project to come up effective solutions to save 50% of cancer

patients in the following 25 years. If the solution to a problem was done right, no matter how

difficult was the challenge, it could be overcome! That was the lesson we learned from the

moonshot project. On the other hand, a simple matter if not done right can become an

unsolvable difficult problem. Obviously, the health profession did not do the right thing on

cancer project to result in failure to save cancer patients. Cytotoxic killing of CCs was the choice

of cancer establishments to combat cancer in the past. If a therapeutic modality has been drilled

through as a presidential project and failed, it was fair to conclude that therapeutic modality

was not good to solve cancer. Cancer establishments, nevertheless, persisted in pursuing the

failed modality of cancer therapy, and the consequence was cancer mortalities remained at

historical high. The goal of President Biden was moderate only to save 50% of cancer patients

in the following 25 years, but a drastic change of therapeutic approaches must be implemented

to achieve that goal.

OPINIONS AND DISCUSSIONS

Cancer Arises as a Consequence of Wound Unhealing

The concept of cancer as an unhealing wound was introduced by the great German scientist

Virchow in the 19th century [3]. It was again brought up by Dvorak in 1986 [4]. The close

relationship between cancer and wound healing was noticed by MacCarthy-Morrough and

Martin [5]. We provided the most important details on this subject that included abnormal MEs

to block differentiation [6-8]; chemo-surveillance as a natural mechanism to ensure perfection

of wound healing to avoid cancer [9-11]; DIs and DHIs as the wound healing metabolites and

also as the active players of chemo-surveillance [9-11]; hypomethylation of nucleic acids as the

most critical mechanism to achieve terminal differentiation of cells with abnormal MEs [12];

the mechanism of wound healing to involve the proliferation and the terminal differentiation

of PSCs [13-15]; and the evolution of CSCs from PSCs due to wound unhealing [16]. Studies

above described clearly show that cancer and wound healing are closely related to involve PSCs

as the common elements. Wound healing requires the proliferation and the terminal

differentiation of PSCs. PSCs are the most primitive stem cells to give rise to the organ or tissue

during embryonic development. A small percentage of these cells are reserved in the organ or

tissue for the need to expand or to repair. They are pluripotent stem cells capable of

differentiation into various cells such as parenchyma and epithelial cells, connective tissues,

and blood vessels needed for the repair of the wound. These cells are protected by drug

resistance and anti-apoptosis mechanisms, and express chemokine receptors to respond

swiftly to signals for expansion or repair. MEs of these cells are abnormal like CCs to associate

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Liau, M. C., Craig, C. L., & Baker, L. L. (2023). Wound Healing Process as the Most Appropriate Modality of Cancer Therapy. European Journal of

Applied Sciences, Vol - 11(1). 463-471.

URL: http://dx.doi.org/10.14738/aivp.111.13904

with telomerase [6-8]. The blockade of differentiation attributable to abnormal MEs may be a

critical mechanism to build up cell mass for the development of fetus or for the repair of wound.

TET-1 enzyme is functional in these normal primitive stem cells to direct lineage transitions.

This enzyme is silenced in CSCs and CCs [16]. The silence of TET-1 enzyme marks the difference

between PSCs and CSCs.

Wound triggers biological and immunological responses. The biological response involves the

release of arachidonic acid (AA) from membrane-bound phosphatidylinositol through

phospholipase A2 for the synthesis of prostaglandins (PGs) by cyclooxygenases and PG

synthases [17, 18]. Although AA and PGs are active as DIs, which are chemical capable of

eliminating telomerase from abnormal MEs [19], the induction of terminal differentiation of

PSCs at the initial stage of wound is not the primary objective of PGs. Rather the localized

inflammation caused by PGs [20] is responsible for the increase of membrane permeability to

facilitate the extravasation of plasma proteins and regulatory factors in the wound resulting in

edema response. Chemo-surveillance mediated through DIs and DHIs, which are inhibitors of

MEs capable of potentiating the activity of DIs, functions as a brake to prevent the build up of

PSCs. These inhibitory components must be released from inside of PSCs in order for PSCs to

build up enough cells to repair the wound. PGs are metabolically unstable [17]. Their biological

effects are most likely brief during the initial phase of wound to promote proliferation of PSCs,

whereas the induction of terminal differentiation of PSCs at the final stage of wound healing is

accomplished by wound healing metabolites, namely DIs and DHIs of chemo-surveillance. Thus,

the functionality of chemo-surveillance is very important to dictate the success of wound

healing [10]. Healthy people can maintain a steady level of DIs and DHIs to ensure perfection of

wound healing. The stable end products of PGs are also active as DIs, although not as active as

PGs [19]. The DI activity of the end products of PGs can be greatly potentiated by pregnenolone

which is a major DHI of chemo-surveillance [19, 21]. When the functionality of chemo- surveillance is intact as in healthy people, wound is usually healed naturally without having to

put up any effort. But if the functionality of chemo-surveillance is damaged due to pathological

conditions, the healing process may be affected to create problems such as ugly scars, tissue

fibrosis, dementia, and the worst of all cancer [15, 22, 23]. Wounds that exhibit impaired

healing frequently enter a state of pathologic inflammation due to a postponed, incomplete, or

uncoordinated healing process [24, 25]. The immunological response of the wound is also a

contributing factor of pathologic inflammation to prompt the production of inflammatory

cytokines which are bad for wound healing, particularly TNF. TNF is also named cachectin after

its effects to produce cachexia symptoms. A characteristic disorder of cachexia symptoms is the

excessive urinary excretion of low molecular weight metabolites because of leaky blood vessels

caused by TNF [26, 27]. Wound healing metabolites DIs and DHIs are among such metabolites

excreted leading to the collapse of chemo-surveillance. Terminal differentiation of PSCs cannot

proceed efficiently to eliminate symptoms caused by wounds, e.g. anemia due to the wound to

hematopoietic cells or hypoxia due to the wound to the lung. The persistent symptoms then

force PSCs to keep on proliferating. PSCs are after all normal stem cells, which obey the rule of

contact inhibition. Evolution into CSCs by silencing of TET-1 enzyme is a way to escape contact

inhibition, which is within the reach of PSCs equipped with abnormally active MEs. But the

differentiation of CSCs is completely blocked without TET-1 enzyme. Symptoms due to wounds

remain unsolved. Additional pressure is then put on CSCs to increase proliferation.

Chromosomal abnormalities such as translocations to activate oncogenes or deletions to