Cancer Etiology: A Metabolic Disease Originating from Life’s Major Evolutionary Transition?

Abstract

A clear understanding of the origins of cancer is the basis of successful strategies for effective cancer prevention and management. The origin of cancer at the molecular and cellular levels is not well understood. Is the primary cause of the origin of cancer the genomic instability or impaired energy metabolism? An attempt was made to present cancer etiology originating from life's major evolutionary transition. The first evolutionary transition went from simple to complex cells when eukaryotic cells with glycolytic energy production merged with the oxidative mitochondrion (The Endosymbiosis Theory first proposed by Lynn Margulis in the 1960s). The second transition went from single-celled to multicellular organisms once the cells obtained mitochondria, which enabled them to obtain a higher amount of energy. Evidence will be presented that these two transitions, as well as the decline of NAD+ and ATP levels, are the root of cancer diseases. Restoring redox homeostasis and reactivation of mitochondrial oxidative metabolism are important factors in cancer prevention.

A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives

“…Furthermore, the intracellular location of the tumor microbiota connects it to some of the most recent theories on the origin of tumors [195,196]. One of these notions sees the roots of cancer etiology as grounded in the two transitions (from prokaryotic to eukaryotic, and from unicellular to multicellular beings) that ultimately lead to the establishment of higher organisms [195]. The other, the so-called "Systemic-Evolutionary Theory of Cancer (SETOC)", proposes that, as a consequence of long-term injuries caused by cancer-promoting factors, cancer results from a process of regression of the eukaryotic cells towards a situation in which its prokaryotic component assumes uncoordinated behaviors, which ultimately break the integration of the components of the endosymbiotic cellular system [196].…”

“…Interestingly, this finding brings us back to the world of prokaryotes that provide specific functions while being intracellular residents, as a possible case of what could be called "oncologic symbiosis". Furthermore, the intracellular location of the tumor microbiota connects it to some of the most recent theories on the origin of tumors [195,196]. One of these notions sees the roots of cancer etiology as grounded in the two transitions (from prokaryotic to eukaryotic, and from unicellular to multicellular beings) that ultimately lead to the establishment of higher organisms [195].…”

Spontaneous and Induced Animal Models for Cancer Research

“…These three enzymes are responsible for distinct steps within the Krebs cycle [223]. In vitro models are most of the time unsuitable for such studies due to reduced numbers of mitochondria or even their absence [224], uncertain mechanisms for oxygen consumption rate [225], and lack of heterogeneity of cultured cells that cannot mimic the entire mitochondrial profile of a primary cancer [226]. For tumor biopsies, results have been obtained from an end point situation with multiple events occurring until intervention, including consequences of carcinogenesis and not necessarily causative effects [223].…”

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

“…Even though cancers have been some of the most widely studied human disorders, their pathophysiology remains unknown, mostly because the mechanisms of disease are highly heterogeneous [ 29 ]. Clearly, the understanding of neoplastic transformation and biological properties of cancer cells would help to improve cancer diagnosis and treatment [ 30 ]. From this perspective, it appears that EVs may be a good candidate as a molecular biomarker of disease activity and treatment monitoring.…”