Restoration of Chemo-Surveillance as a Top Priority to Save Cancer Patients
Published: 2023-11-07
Page: 227-237
Issue: 2023 - Volume 6 [Issue 2]
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.
*Author to whom correspondence should be addressed.
Abstract
Cancer mortality is very high and is still increasing. The objective of this study is to rely on the restoration of chemo-surveillance to reduce cancer mortality called for by President Biden in his cancer moonshot initiative speech last year. The reason cancer mortality remains so high is that we are not pursuing the right approach on cancer therapy. Cancer is caused by wound unhealing due to the collapse of chemo-surveillance. Chemo-surveillance is the nature’s creation of allosteric regulation to keep cells with abnormal methylation enzymes (MEs) under control. Wound healing comes naturally because the nature creates chemo-surveillance to ensure the perfection of wound healing. Wound healing requires the proliferation and the terminal differentiation of progenitor stem cells (PSCs). Efficient differentiation of PSCs is a critical mechanism of wound healing. MEs play an essential role in the regulation of cell replication and differentiation. In telomerase-expressing cells, MEs are associated with telomerase to alter the kinetic properties of MEs and the regulation in favour of cell growth, which is important for wound healing. Chemo-surveillance is an important safety mechanism to avoid unnecessary build-up of cells with abnormal MEs to cause clinical symptoms such as tissue fibrosis, dementia, organ failure and cancer. Chemo-surveillance can be destroyed under pathological conditions producing elevated tumor necrosis factor (TNF) to cause cachexia symptoms resulting in the collapse of chemo-surveillance. PSCs are then forced to evolve into cancer stem cells (CSCs) by a single hit to silence the TET-1 enzyme to escape contact inhibition which limits the extent of PSCs to build up. The inability of CSCs to undergo terminal differentiation due to the collapse of chemo-surveillance eventually forces CSCs to progress to faster-growing cancer cells (CCs) through chromosomal abnormalities such as translocations or deletions to activate oncogenes or to inactivate suppressor genes to become full-blown cancer. Obviously, the collapse of chemo-surveillance is a critical event in the development of cancer, restoration of chemo-surveillance is, therefore, an easy and effective solution to save cancer patients.
Keywords: Allosteric regulation, chemo-surveillance, cancer therapy, CSCs, PSCs, wound healing
How to Cite
References
Google search on cancer statistics-NCI and American Cancer Society.
Liau MC, Fruehauf JP. It has been half a century since President Nixon declared war on cancer: Destabilization of abnormal methylation enzymes has the blessing of the nature to win the war on cancer. Adv Complement Alt Med. 2020;6(1):538-539.
Liiau MC, Craig CL. Wound healing metabolites to heal cancer and unhealed wounds. Intl Res J Oncol. 2022;6(3):8-20.
Liau MC, Craig CL, Baker LL. CDA formulations to fulfill cancer moonshot and to win the war on cancer. Int J Res Oncol. 2023;2(2):1-8.
Liau MC, Szopa M, Burzynski B, Burzynski SR. Chemo-surveillance: A novel concept of the natural defense mechanism against cancer. Drugs Exptl Clin Res. 1989;13(Suppl.1):72-82.
Liau MC, Baker LL. The functionality of chemo-surveillance dictates the success of wound healing as well as cancer therapy. Nov Res Sci. 2021:7(2):1-3.
Liau MC, Craig CL. Chemo-surveillance as a natural mechanism to ensure perfection of wound healing to avoid cancer evolution and to cure cancer. In: New Horizons in Medicine and Medical Research. 2022;6(3).
ISBN: 978-93-5547-4.
Liau MC, Craig CL, Baker LL. Wound unhealing as a grave issue of cancer. Intl Res J Oncol. 2023;6(1):97-103.
Liau MC, Craig CL, Liau LL. Abnormal methylation enzymes as the most critical issue of cancer. Intl Res J Oncol. 2023;6(2):168-176.
Liau MC, Lee SS, Burzynski SR. Modulation of cancer methylation complex isozymes as a decisive factor in the induction of terminal differentiation mediated by Antineoplaston A5. Intl J Tiss React. 1990;12(Suppl.):17-36.
Liau MC, Liau CP, Burzynski SR. Potentiation of indued terminal differentiation by phenylacetic acid and related chemicals. Intl J Exptl Clin Chemother. 1992;5:9-17.
Liau MC, Craig CL. On the mechanism of wound healing and the impact of wound on cancer evolution and cancer therapy. Intl Res J Oncol. 2021;5(3):25-31.
Liau MC, Fruehauf JP. Restoration of the chemo-surveillance capability is essential for the success of chemotherapy and radiotherapy to put cancer away. Adv Complement Alt Med. 2019;5(4):474-475.
Liau MC, Baker LL. Destruction promotes the proliferation of progenitor stem cells and cancer stem cells. Therefore, non-destruction is a better strategy for cancer therapy. J Pharmacol Pharmaceu Pharmacovigi. 2020;4:029.
DOI: 10.24966/PPP-5649/100029
Liau MC, Craig CL, Baker LL. Wound healing process as the most appropriate modality of cancer therapy. Eur J Applied Sci. 2023;11(1):463-471.
Liau MC, Fruehauf JP. The winner of the contest to eradicate cancer stem cells wins the contest of cancer therapies: The winner is cell differentiation agent formulations. Adv Complement Alt Med. 2020;5(4):476-478.
Liau MC, Fruehauf PA, Zheng JH, Fruehauf JP. Development of synthetic cell differentiation agent formulations for the prevention and therapy of cancer via targeting of cancer stem cells. Cancer Stu Ther J. 2019;4(1):1-15.
Liau MC, Baker LL. Eradication of cancer stem cells to win the war on cancer. Nov Res Sci. 2021;6(5):1-3.
Liau MC, Zhuang P, Chiou GCY. Identification of the tumor factor of abnormal methylation enzymes as the catalytic subunit of telomerase. Clin Oncol Cancer Res. 2010:7(2):86- 96.
Liau MC, Chang CF, Giovanella BC. Demonstration of an altered S-adenosylmethionine synthetase in human malignant tumors xenografted into athymic nude mice. J Natl Cancer Inst. 1980;64(5):1071-1075.
Liau MC. Abnormal methylation enzymes: A selective molecular target for differentiation therapy of cancer. Chin Pharm J. 2004;56(2):57-67.
Liau MC. Pharmaceutical composition inducing cancer cell differentiation and the use for treatment and prevention of cancer. US Patent 7232578.B2; 2007.
Liau MC, Kim JH, Fruehauf JP. Destabilization of abnormal methylation enzymes: Nature’s way to eradicate cancer stem cells. Online J Complement Alt Med. 2019;2(5). DOI: 10.33552/OJCAM.2019.02.000456
Liau MC, Kim JH, Fruehauf JP. Destabilization of abnormal methylation enzymes to combat cancer: The nature’s choice to win the war on cancer. Lambert Academic Publishing. 2020;978-620-2-65889-7.
Liau MC, Fruehauf PA, Zheng ZH, Fruehauf JP. Destabilization of abnormal methylation enzymes as an effective therapeutic strategy via induction of terminal differentiation to take out both cancer stem cells and cancer cells. In: Current Aspects in Pharmaceutical Research and Development. 2021;2,(11):120-142.
ISBN 978-93-5547- 055-3 DOI: 10.9734-bpi/caprd/v2/13544D
Liaiu MC, Baker LL. Eradication of cancer stem cells to win the war on cancer. Nov Res Sci. 2022;6(5):1-3.
Liau MC, Fruehauf JP. Winning formulas to fulfill cancer moonshot. Intl J Res Oncol. 2022;1(1):1-5.
Liau MC, Fruehauf JP. Cancer moonshot : Moonshot as a magic code to guide successful solutions of tough challenges such as Cancer. Intl J Res Oncol. 2023;2(1):1- 5.
Liau MC, Craig CL, Baker LL. CDA formulations to fulfill cancer moonshot and to win the war on cancer. Int J Res Oncol. 2023;2(2):1-8.
Liau MC, Baker LL. Abnormal methylation enzymes as the bullseye of targeted cancer therapy. Nov Res Sci. 2021;7(4):1-3.
Liau MC, Craig CL, Baker LL. Exceptional allosteric regulation of methylation enzymes. In: Saraydin Su (edi) : Novel Research Aspects in Medicine and Medical Science. 2023;4:39-56.
Racanelli AC, Turner FB, Xie LY, Taylor SM, Moran RG. A mouse gene that coordinate epigenetic controls and transcriptional interference to achieve tissue spedific expression. Mol Cell Biol. 2008;28(2):836- 848.
Liau MC, Hunt ME, Hurlbert RB. Role of ribosomal RNA methylases in the regulation of ribosome production. Biochemistry. 1976;15(14):3158-3164.
Bernstein KA, Bleichert F, Bean JM, Cross FR, Baserga SJ. Ribosome biogenesis is sensed at the start cell cycle check point. Moll Biol Cell. 2007;18(3):953-964.
Justilien Y, Ali SA, Jamieson L, Yin N, Cox AD, Der CJ, et al. Ect2-dependent rRNA synthesis is required for KRAS-TRP53-driven lung adenocaecinoma. Cancer Cell. 2017;31(2):256-269.
Liau MC, Chang CF, Saunders GS, Tsai YH. S-Adenysylhomocysteine hydrolases as the primary target enzymes in androgen regulation of methylation complexes. Arch Biochem Biophys. 1981;208(1):261-272.
Prudova A, Bauman Z, Braun A, Vitvitsky V, Lu SC, Banerjee R. S-Adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity. Proc Natl Acad Sci USA. 2006;103(17):6489-6494.
Chiba P, Wallner C, Kaizer E. S-Adenosylmethionine metabolism in HL-60 cells: Effect of cell cycle and different6iation. Biochim Biophys Acta. 1988;971(1):38-45.
Liau MC, Baker LL. The impact of COVID-19 pandemic on cancer patients. Intl Res J Oncol. 2022;6(1):97-103.
Liau MC, Craig CL. No scar as an indication of perfect wound healing, ugly scar as imperfect wound healing and cancer as failed wound healing. J Cancer Tomor Intl. 2022;12(1):29-34.
Liau MC, Chang CF, Becker FF. Alteration of S-adenosylmetnionine synthetases during chemical hepatocarcinogenesis and in resulting carcinomas. Cancer Res. 1979;39:2113-2119.
Kamparath BN, Liau MC, Burzynski B, Burzynski SR. Protective effect of Antineoplaston A10 in hepatocarcinogenesis induced by aflatoxin B1. Intl J Tiss React. 1990;12(Suppl.):43-50.
Liau MC, Szopa M, Burzynski B, Burzynski SR. Quantitative assay of pleasma and urinary peptides as an aid for the evaluation of patients undergoing Antineoplaston therapy.Drugs Exptl Clin Res. 1987:13(Suppl.):61-70.
Ho ATV, Palla AR, Blake MR, Yual ND, Wang YX, Magmusson KEG, et al. Prostaglandin E2 is essential for efficacious skeletal muscle stem function, augmenting regeneration and strength. Proc Natl Acad Sci USA. 2017;114(26):6675-6684.
Liau MC, Kim JH, Fruehauf JP. Arachidonic acid and its metabolites as the surveillance differentiation inducers to protect healthy people from becoming cancer patients. Clin Pharmacol Toxicol Res. 2021;4(1):7- 10.
Williamson PJ, Kruger AR, Reynolds PJ, Hamlin TJ, Oscier DG. Establishing the incidence of myelodysplastic syndromes. Br J Haemato. 1994;87(4):743-745.
Boula A, Vougarelis M, Giannouli S, Katrinakis G, Psyllaki M, Pontikoglou C, et al. Effect of CA2 of antitumor necrosis factor-alpha antibody therapy on hematopoiesis of patients with myelodysplastic syndromes. Cliin Cancer Res. 2006;12(10):3099-3108.
Itkin T, Rafii S. Leukemia cells ”gas up” leaky bone marrow blood vessels. Cancer Cell. 2017;32(3):276-278.
Passaro D, Di Tullio A, Abarrategi A, Rousault-Piierre K, Foster K, Ariza-McNaughton L, et al. Increased vascular permeability in the bone marrow microenvironment contributes to disease progression and drug response in acute myeloid leukemia. Cancer Cell 2017;32(3):324-341.
Woll PS, Kjallquist U, Chowdhury O, Doolittle H, Wedge DC, Thongjuea S, et al. Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell. 2014;25(6):794- 808.
Santi DV, Norment A, Garrett CE. Covalent bond formation between a DNA-cytosine methylatransferase of DNA containing 5-azacytosine. Proc Natl Acad Sci USA. 1984;81(22):6993- 6997.
Ma J. Differentiation therapy of malignant tumor and leukemia. CSCO Treaties on the education of clinical oncology. 2007;480-486.
Prassana P, Shack S, Wilson VL, Samid D. Phenylacetate in chemoprevention of 5-aza-2’-deoxycytidine-induced carcinogenesis. Clin Cancer Res. 1995;1(18):865-871.
Gaudet F, Hodgson JG, Eden A, Jackson-Grusby L, Dausman J, Gray JW, et al. Induction of tumor in mice by genomic hypomethylation. Science. 2003:300(5618):489-492.
Palii SS, van Emburgh BO, Sannkpal UT, Brown KD, Robertson KD. DNA methylation inhibitor 5-aza-2’-deoxycytidine induces reversible DNA damage that is distinctly influenced by DNA-methyltransferase 1 and 3B. Mol Cell Biol. 2008;28(2):752-771.
Kizietepe T, Hideshima T, Catley L, Raje N, Yasui H, Shiraishi N, et al. 5-Azacytidine, a methyltransferase inhibitor, induces ATR-mediated DNA-double strand break responses, apoptosis and synergistic cytotoxicity with doxorubicine and bortezomib against multiple myeloma cells. Mol Cancer Ther. 2007;6(6):1718-1727.
Yang Q, Wu F, Wang F, Cai K, Zhang Y, Sun Q, et al. Impact of DNA methyltransferase inhibitor, 5-azacytidine on cardiac development of zebrafish in vivo and cardiomyocyte proliferation, apoptosis, and the homeostasis of gene expression in vitro. J Cell Biochem. 2019;120(10):17459- 17471.
Virchow R. Die Cellular pathologie in ihrer begrundung auf physiologische und pathologische gewebelehve. Hirschwald. 1858;16:400.
Dvorak HF. Tumors: Wounds that do not heal. N Engl J Med. 1986;315(26):1650-1659.
MacCarthy-Morrough L, Martin P. The hallmarks of cancer are also the hallmarks of wound healing. Science Signaling. 2020;13:648.
Liau MC, Lin GW, Hurlbert RB. Partial purification and characterization of tumor and liver S-Adenosylmethionine synthetases. Cancer Res. 1977;37(2):427-435.
Liau MC, Lee SS, Burzynski SR. Hypomethylation of nucleic acids: A key to the induction of terminal differentiation. Intl J Exptl Clin Chemother. 1989;2:187-199.
Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, et al. Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. Cancer Sci. 2012;103(4):670-676.
Ficz GM, Gibben JG, Loss of 5-hydroxmethylcytosine in cancer: Cause or consequence? Genomics. 2011;104(5): 352-357.
Liau MC, Baker LL. Cancer patients’ lives matter. Adv Complement Alt Med. 2021;6(5):638-640.