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Molecular Research on Metabolic Aberration-Driven Carcinogenesis

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 30 December 2026 | Viewed by 708

Special Issue Editor


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Guest Editor
Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33101, USA
Interests: obesity associated carcinogenesis; adipocytokines; adipose tissue microenvironment; metabolic disorder; carcinogenesis

Special Issue Information

Dear Colleagues,

This Special Issue aims to bridge the gap between metabolic disorders and the formation and accumulation of carcinogenic mutations. Metabolic syndrome, which includes obesity, insulin resistance, dyslipidemia, and hypertension, is increasingly recognized as a major risk factor for a wide range of mutation-driven epithelial cancers.

Epidemiological and experimental evidence suggests that metabolic interventions—including weight loss, bariatric surgery, metformin, and aspirin—can significantly reduce the incidence of obesity-associated cancers. The economic burden of these cancers, through both healthcare costs and productivity loss, is projected to become a global crisis by 2050.

The hereditary metabolic disorder Perutz–Jaeger Syndrome, which confers a 15-fold increase in cancer risk, highlights the crucial role of AMPK, a central metabolic regulator also impaired in obesity. This underscores the need to understand how energy imbalance affects genomic integrity and promotes oncogenesis.

However, the molecular mechanisms linking metabolic dysfunction to carcinogenesis remain incompletely understood.

We invite submissions of the following:

  • Original research articles, reviews, and short communications examining the following:
    • Mutation accumulation and expression;
    • Cell signaling and energy stress;
    • Inflammation, apoptosis, and DNA repair;
    • Epigenetic modifications and chromatin dynamics;
    • The role of AMPK and related metabolic signaling nodes.
  • Studies using the following:
    • Molecular biology methods;
    • High-throughput omics: genomics, transcriptomics, proteomics, and metabolomics;
    • Computational biology, modeling, and systems biology;
    • Translational or preclinical cancer models.

We especially encourage the following:

  • Interdisciplinary collaborations across metabolism, cancer biology, and genomics;
  • Research offering mechanistic insights or novel therapeutic strategies targeting the metabolic–genomic interface.

Best regards,

Prof. Dr. John Joseph Byrnes
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolic disorders
  • carcinogenic mutations
  • carcinogenesis
  • obesity-associated cancers
  • metabolic signaling

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Published Papers (1 paper)

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Review

20 pages, 1252 KB  
Review
Selective Inhibition of Proofreading Exonucleases: The Central Role in Obesity-Associated Carcinogenesis
by John J. Byrnes
Curr. Issues Mol. Biol. 2026, 48(4), 346; https://doi.org/10.3390/cimb48040346 - 26 Mar 2026
Viewed by 507
Abstract
Obesity-associated carcinogenesis offers a model to explore the transition from metabolic dysregulation to genomic instability and carcinogenesis. Adenosine 5′-monophosphate-activated protein kinase (AMPK), the principal cellular energy sensor, coordinates adenosine triphosphate (ATP) production with metabolic demand; however, in obesity, AMPK activity is impaired, resulting [...] Read more.
Obesity-associated carcinogenesis offers a model to explore the transition from metabolic dysregulation to genomic instability and carcinogenesis. Adenosine 5′-monophosphate-activated protein kinase (AMPK), the principal cellular energy sensor, coordinates adenosine triphosphate (ATP) production with metabolic demand; however, in obesity, AMPK activity is impaired, resulting in reduced ATP, elevated Adenosine Monophosphate (AMP), and cellular energy stress. Deoxyribonucleic Acid (DNA) polymerases ε (Pol ε) and δ (Pol δ) maintain replication fidelity via a 3′→5′ exonuclease proofreading activity that removes misincorporated nucleotides. Elevated AMP directly binds and selectively inhibits the exonucleases, conserving energy at the expense of genomic accuracy. As a result, replication errors escape correction and accumulate, some conferring a selective advantage and driving carcinogenic evolution. Therapeutic and lifestyle interventions that activate AMPK—including weight loss, exercise, metformin, and aspirin—restore ATP production, lower AMP, and relieve inhibition of exonuclease proofreading, thereby preserving genomic integrity and slowing mutation-driven carcinogenesis. This framework reveals two core biological principles: 1. Energy metabolism and DNAreplication fidelity are mechanistically coupled at the DNA polymerase active site. 2. The mutation rate is an adaptive metabolic phenotype, modulated by AMP levels. These concepts redefine the metabolic–genetic interface in carcinogenesis and highlight AMPK activation as a rational target for obesity-associated cancer prevention. Full article
(This article belongs to the Special Issue Molecular Research on Metabolic Aberration-Driven Carcinogenesis)
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