Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Biochemistry, Not Oncogenes, may Demystify and Defeat Cancer

Version 1 : Received: 19 April 2021 / Approved: 22 April 2021 / Online: 22 April 2021 (09:37:10 CEST)
Version 2 : Received: 4 July 2021 / Approved: 6 July 2021 / Online: 6 July 2021 (11:32:47 CEST)
Version 3 : Received: 27 December 2021 / Approved: 28 December 2021 / Online: 28 December 2021 (10:53:54 CET)

A peer-reviewed article of this Preprint also exists.

Kulsh, J. Biochemistry—Not Oncogenes—May Demystify and Defeat Cancer. Oncology and Therapy 2023, doi:10.1007/s40487-023-00221-y. Kulsh, J. Biochemistry—Not Oncogenes—May Demystify and Defeat Cancer. Oncology and Therapy 2023, doi:10.1007/s40487-023-00221-y.

Abstract

Presence of mutated genes strongly correlates with incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprit, we need to look at the biochemistry of cancer, with focus on enzymes which carry out any and all transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) which is tightly linked to tumor growth. Beside the circumstantial evidence that cancer is induced at its vulnerable active-site by various carcinogens, there exists experimental proof of its role in initiating retinoblastoma and HPV-related cervical cancers. Blocking the activity of RnR is a certain way to arrest cancer.

Keywords

cancer; DNA sequencing; DNA synthesis; enzyme; free-radicals; genome; HPV; oncogenes; retinoblastoma; ribonucleotide reductase; RnR; SMT; TCGA

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Comments (2)

Comment 1
Received: 30 April 2021
Commenter: Dr. Rajib Sengupta
The commenter has declared there is no conflict of interests.
Comment: That's a very interesting article. As a biochemist, my viewpoints are also saying the same thing related to the redox biochemistry of Cancer. RNR is a very interesting enzyme system with R1 and R2 subunits. We need to have more research on the redox regulations of different subunits. Moreover, the it's relation to thioredoxin and glutaredoxin systems make in more complex and fascinating. This article clearly shows the significance of RNR system related to cancer-related drug designing and therapies.
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Comment 2
Received: 6 May 2021
Commenter: Elizabeth Sandidge Evans
The commenter has declared there is no conflict of interests.
Comment: This article is very interesting. I have only anecdotal comments to make:
1. My best friend's father worked at Dow Chemical during the Vietnam War. He used to stand in napalm fixing equipment. The family dog who slept on his work boots died of cancer, the wife died in her late 50s of cancer, but her father lived to be much older. He had an ostomy bag for waste elimination and a team of Japanese scientists came to visit him to see why he was still alive. He was from old "tarheel" stock from North Carolina. He may have had a little Native American ancestry, but he also had Caucasian stock.
2. I grew up near Langley Air Force base in Hampton Va. The Air Force at Langley regularly sprayed DDT from an airplane every summer. The idea was to combat mosquitos. My Mom died of pancreatic cancer at the age of 63, but my father lived to be 93.
I am interested in the effect of genetics on the survival rate of people exposed to high levels of toxins, so your article is very interesting to me. Thank you for sharing it.
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Comment 3
Received: 17 May 2021
Commenter:
The commenter has declared there is no conflict of interests.
Comment: (This is the author.) There is a spelling mistake: 'heterogenous' should be 'heterogeneous' in section 2.3. In the next version, that section will also be slightly expanded, pointing to new references.
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