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The paper emphasizes cancer biochemistry, focusing on transformation-facilitating enzymes, especially ribonucleotide reductase, whose activity links to tumor growth and can be targeted to arrest 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does the article argue that genes alone may not explain cancer initiation or progression?","Question",{"text":63,"@type":64},"It notes that decades of research have not yielded specific causative genes for most cancers and that epidemiological studies consistently suggest the environment plays the principal role in causing cancer.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What does the article identify as a central biochemical focus for understanding and controlling cancer?",{"text":68,"@type":64},"It emphasizes enzymes involved in cellular transformations, particularly the rate-limiting enzyme ribonucleotide reductase (RnR), whose activity is tightly linked to tumor growth.",{"name":70,"@type":61,"acceptedAnswer":71},"How does the article propose targeting cancer using ribonucleotide reductase?",{"text":72,"@type":64},"It argues that malignant RnR activity can be blocked to arrest cancer, including by disabling its vulnerable free-radical-containing active site in a 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\nREVIEW  \nBiochemistry—Not Oncogenes—May Demystify and Defeat Cancer  \nJay Kulsh   \nReceived: December 12, 2022/Accepted: January 24, 2023 /Published online: February 13, 2023 􀀂 The Author(s) 2023  \nABSTRACT  \nThe presence of mutated genes strongly correlates with the 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 culprits, we need to look at the biochemistry of cancer, with a focus on enzymes that invariably facilitate transformations in a cell. In particular, attention should be  \npaid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR), whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active site by various carcinogens, its role in initiating retinoblastoma and human papillomavirus (HPV)-related cervical cancers has been well documented in recent years. Blocking the activity of malignant RnR is a certain way to arrest cancer.  \nKeywords: Carcinogenesis; Cancer treatment; Cervical cancer; DNA synthesis; Free radical; Retinoblastoma; Ribonucleotide reductase (RnR); Somatic mutation theory (SMT)  \nJ. Kulsh (&)  \nIndependent Scientist, Los Angeles, CA, USA  \ne-mail: [jkulsh@gmail.com](jkulsh@gmail.com)  \nKey Summary Points  \nFor the vast majority of cancers, the genetic theory is inadequate in explaining initiation or progression of the disease.  \nMany ‘‘tumor suppressor genes’’ have been identified but ‘‘cancer-causing oncogenes’’remain elusive.  \nSince carcinogenic chemicals cause most cancers, we examined cancer biochemistry, with a focus on enzymes that invariably mediate cellular transformations.  \nHyperactivity of the ribonucleotide reductase (RnR) enzyme is implicated inretinoblastoma and HPV cancers; furthermore, its active site is vulnerable to carcinogens—making it a likely epicenter of cancer.  \nThe free-radical-containing active site of RnR can be disabled biophysically, resulting in a non-toxic cancer treatment.  \nIn 2005, at the onset of The Cancer Genome Atlas (TCGA) program, Dr. Eric C. Lander, director of Broad Institute of MIT and Harvard, declared in New York Times,‘‘Knowing the defects of the cancer cell points you to the Achilles’ heel of tumors’’  \n[1] .  \nAt Cancer World 2013, Nobel laureate James Watson opined, ‘‘We can carry on and sequence every piece of DNA that ever existed, but I don’t think we will find any Achilles heels [of cancer]’’ [2] .  \nINTRODUCTION—CANCER WAR NOT WON  \nThe year 2021 marked the 50th anniversary of the declaration of ‘‘war on cancer’’ by US President Nixon. He was inspired by President  \nKennedy’s declared goal in 1961 to land a manon the Moon by the end of the decade—which had come true, to international acclaim. However, progress in the field of cancer has been quite limited, despite plentiful funding over the last five decades.  \nThe overall survival rates have improved, to varying degrees, for all cancers, primarily due to early detection and intervention. Preventative measures, such as the reduced use of tobacco products, have also lowered the incidences of lung cancers [3] . However, effective treatment remains out of reach for most cancers.  \nCommon reasons given for this slow progress is that cancer is a very complex disease—and that it may not be one but many diseases. However, there is another possibility, raised as early as 1994 by","cbCaiiJv2epF7rlM","https://ap.wps.com/l/cbCaiiJv2epF7rlM","pdf",992464,17,"English","# Abstract\n# Key Summary Points\n# Introduction—Cancer War Not Won\n# Essence of the Gene-Centric View of Cancer","[{\"question\":\"Why does the article argue that genes alone may not explain cancer initiation or progression?\",\"answer\":\"It notes that decades of research have not yielded specific causative genes for most cancers and that epidemiological studies consistently suggest the environment plays the principal role in causing cancer.\"},{\"question\":\"What does the article identify as a central biochemical focus for understanding and controlling cancer?\",\"answer\":\"It emphasizes enzymes involved in cellular transformations, particularly the rate-limiting enzyme ribonucleotide reductase (RnR), whose activity is tightly linked to tumor growth.\"},{\"question\":\"How does the article propose targeting cancer using ribonucleotide reductase?\",\"answer\":\"It argues that malignant RnR activity can be blocked to arrest cancer, including by disabling its vulnerable free-radical-containing active site in a biophysically non-toxic way.\"}]","Biochemistry—Not Oncogenes—May Demystify and Defeat Cancer | PDF",1790227774,43]