Cancer: Tumor Iron Metabolism, Mitochondrial Dysfunction and Tumor Immunosuppression; “A Tight Partnership—Was Warburg Correct?”

Abstract

Over the last 30 years there have been numerous worldwide investigators involved in cancer research. Billions of dollars have been spent on drug development and cancer research; however, with all of the new agents and modalities of treatment, we have honestly not significantly improved the overall survival of the Stage IV cancer patient. There is and will not be a magic bullet treatment, thus the extensive title of this paper. We are convinced that unless we use multiple innovative therapies in combination with conventional treatment, we will never truly defeat this disease. We have attempted to address this problem by presenting in detail some of these complex mechanisms involved in tumorigenesis, progression, escape, and metastasis. Most investigators have their own special area of interest, but if we are to conquer this scourge, we must develop an extensive, multifaceted, comprehensive approach. Hopefully this article will contribute to awareness and further insight into this very serious and complicated problem, so we can improve quality of life and improve the survival of the Stage IV cancer patient.

Stomach Cancer: Interconnection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth

“…Reactive oxygen and nitrogen species (ROS/RNS) are considered as potential diagnostic and prognostic markers in many types and stages of cancer and targets for the therapeutic treatments [5][6][7][8][9]. For example, depending on the generation rate, duration of exposure, localization, and types of the metabolites that can be produced, superoxide radicals (O 2…”

Electron Paramagnetic Resonance Study of Tumor Affected Bone Marrow

“…Tumor iron metabolism and mitochondrial dysfunction are considered as the major players in tumorigenesis [15]. Tumor cells undergoing profound changes in their own intrinsic metabolism affect the microenvironment.…”

“…[4]). Speaking present-day language-with a pool of loosely bound iron, which is termed the labile iron pool (LIP) [14,15]. Released due to the destructions of different proteins and ironcontaining compartments, a "free" iron binds with the diverse low-molecular weight substances as phosphate, nucleotides, hydroxyl, amino and sulfhydryl groups, etc.…”

Want to Cure Cancer? Then Revisit the Past; “Warburg Was Correct”, Cancer Is a Metabolic Disease

“…I discussed this in detail in a recent article [12] and will address it again later in this communication. I am convinced that mitochondrial dysfunction (impaired cellular respiration) leading to aerobic fermentation is also related to tumor iron metabolism and stabilization of the transcription factor Hypoxia Inducible factor-1alpha (HIF1-a), which plays a major role in both.…”

“…These six alterations were: 1) self-sufficiency in growth signals, 2) insensitivity to inhibitory growth signals, 3) evasion of apoptosis, 4) limitless replicative potential, 5) sustained vascularity (angiogenesis), and 6) tissue invasion and metastasis. Seyfried, others and I believe that in addition to these six recognized hallmarks of cancer, the "Warburg Effect" or aerobic fermentation is also a very robust metabolic hallmark of most tumors [7]- [12].…”