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Molecular Markers of Tumor Response and Toxicity of Antitumor Therapy
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Molecular Markers of Tumor Response and Toxicity of Antitumor Therapy

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: 31 March 2027 | Viewed by 4384

Editors

Prof. Dr. Liudmila V. Spirina

E-Mail Website
Guest Editor
Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia
Interests: oncogenesis; gastric cancer; colorectal cancer; biochemistry of cancers; molecular oncology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Natalya V. Yunusova

E-Mail Website
Guest Editor
Laboratory of Tumor Biochemistry, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia
Interests: colorectal cancer; ovarian cancer; breast cancer; gliomas; molecular oncology; cell biology; extracellular vesicles; obesity; neurotoxiсity; cardiotoxiсity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Contemporary oncology has achieved substantial advancements, yet a pivotal challenge persists: the absence of universally applicable, pathogenetically grounded biomarkers to accurately forecast tumor response to treatment, evaluate individual susceptibility to adverse effects, and tailor therapy based on molecular characteristics. Despite standardized treatment protocols, therapeutic outcomes exhibit considerable heterogeneity, ranging from complete remission to disease progression or stabilization. Moreover, side effects often necessitate dose adjustments or treatment interruptions, further undermining treatment efficacy. The lack of predictive biomarkers for toxicity prior to initiation of therapy precludes the optimization of treatment regimens, thereby limiting the potential for personalized therapeutic strategies.

Within the confines of a single histological classification, tumors display molecular heterogeneity, which significantly influences their sensitivity to various therapeutic modalities. Current staging systems do not adequately capture this biological complexity.

Molecular biomarkers, encompassing genes, proteins, metabolites, circulating markers (extracellular vesicles, free DNA and RNA, nucleoprotein complexes) and epigenetic modifications, hold the key to predicting treatment response, assessing toxicity risk, monitoring disease progression, and formulating individualized treatment plans. The Special Issue "Molecular Markers of Tumor Response and Toxicity of Antitumor Therapy" aims to synthesize the latest scientific insights into molecular predictors. Its primary objective is to identify critical research areas that can facilitate the transition from empirical to precision-based treatment selection in oncology.

Prof. Dr. Liudmila V. Spirina
Prof. Dr. Natalya V. Yunusova
Guest Editors

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-anonymized 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 2400 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

  • anti-cancer therapy
  • side effect
  • tumor response
  • toxicity
  • molecular markers

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Published Papers (4 papers)

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Research

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16 pages, 12872 KB  
Article
Elevated Tumor HIF-1α Expression Correlates with Advanced Pathological Stage Following Neoadjuvant Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma
by Hsin-Yi Shih and Chien-Chih Chen
Curr. Issues Mol. Biol. 2026, 48(5), 525; https://doi.org/10.3390/cimb48050525 - 18 May 2026
Viewed by 449
Abstract
Tumor hypoxia has been implicated in treatment resistance and disease progression in esophageal squamous cell carcinoma (ESCC), yet its relationship with post-neoadjuvant pathological staging remains unclear. This study evaluated the association between hypoxia-inducible factor-1α (HIF-1α) expression and pathological stage following neoadjuvant concurrent chemoradiotherapy [...] Read more.
Tumor hypoxia has been implicated in treatment resistance and disease progression in esophageal squamous cell carcinoma (ESCC), yet its relationship with post-neoadjuvant pathological staging remains unclear. This study evaluated the association between hypoxia-inducible factor-1α (HIF-1α) expression and pathological stage following neoadjuvant concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 55 patients with ESCC treated with standardized neoadjuvant CCRT followed by curative esophagectomy. Immunohistochemical staining was performed on surgical specimens to assess tumor (HIF-T%) and stromal (HIF-N%) HIF-1α expression, and correlations with postoperative pathological stage were analyzed. Tumor HIF-1α expression was significantly higher in patients with pathological stage III disease compared with stage I–II disease (40% vs. 15%, p = 0.023). Increasing trends in tumor HIF-T% were observed across higher T and N classifications, although these did not reach statistical significance. Stromal HIF-1α expression was not associated with pathological stage. These findings demonstrate that elevated tumor HIF-1α expression is associated with advanced pathological stage following neoadjuvant CCRT in ESCC, supporting the role of hypoxia-related signaling in treatment resistance. HIF-1α may serve as a clinically relevant biomarker of residual disease burden, although further validation in larger cohorts is warranted. Full article
(This article belongs to the Special Issue Molecular Markers of Tumor Response and Toxicity of Antitumor Therapy)
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Review

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21 pages, 925 KB  
Review
MALDI-TOF Mass Spectrometry for Glioblastoma Secretome Biomarker Screening: A Review of Challenges and Perspectives
by David Aebisher, Klaudia Dynarowicz, Rostyslav Marunych, Izabela Rudy, Kacper Rogóż, Aleksandra Kawczyk-Krupka, Piotr Oleś and Dorota Bartusik-Aebisher
Curr. Issues Mol. Biol. 2026, 48(6), 627; https://doi.org/10.3390/cimb48060627 - 16 Jun 2026
Viewed by 473
Abstract
Glioblastoma (GBM) remains one of the most aggressive malignancies, characterized by profound heterogeneity and a dismal prognosis. While genomic and transcriptomic profiling have provided structural insights, they often fail to capture the dynamic interactions within the tumor microenvironment (TME). Secretome analysis—the study of [...] Read more.
Glioblastoma (GBM) remains one of the most aggressive malignancies, characterized by profound heterogeneity and a dismal prognosis. While genomic and transcriptomic profiling have provided structural insights, they often fail to capture the dynamic interactions within the tumor microenvironment (TME). Secretome analysis—the study of proteins actively secreted by tumor cells—offers a functional readout of these interactions and a reservoir for potential biomarkers. In this review, we critically evaluate the role of MALDI-TOF Mass Spectrometry as a strategic tool for GBM secretome profiling. While Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) remains the gold standard for deep protein discovery, we argue that MALDI-TOF’s speed, cost-effectiveness, and high-throughput capabilities position it as an ideal platform for clinical screening and “spectral phenotyping.” We discuss the technical hurdles, such as ion suppression and the “leakome” (intracellular contamination), and highlight how integrating MALDI with Extracellular Vesicle (EV) enrichment and Artificial Intelligence (AI) can bridge the gap between in vitro discovery and clinical application. Full article
(This article belongs to the Special Issue Molecular Markers of Tumor Response and Toxicity of Antitumor Therapy)
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30 pages, 1202 KB  
Review
Omics-Derived Prognostic Biomarkers in Tongue Squamous Cell Carcinoma: A Systematic Review with Risk-of-Bias Appraisal and Translational Prioritization
by Ioannis Astreidis, Ilias Kostidis, Andigoni Malousi, Konstantinos Paraskevopoulos, Dimitrios Andreadis, Konstantinos Vahtsevanos and Ioannis Vizirianakis
Curr. Issues Mol. Biol. 2026, 48(4), 389; https://doi.org/10.3390/cimb48040389 - 10 Apr 2026
Cited by 2 | Viewed by 1189
Abstract
Tongue squamous cell carcinoma (TSCC) is clinically heterogeneous, and patients with a similar TNM stage can experience markedly different outcomes. We systematically reviewed omics-driven studies to identify prognostic TSCC biomarkers. Although fundamentally prognostic, we discussed their theoretical translational relevance regarding future clinical decisions—such [...] Read more.
Tongue squamous cell carcinoma (TSCC) is clinically heterogeneous, and patients with a similar TNM stage can experience markedly different outcomes. We systematically reviewed omics-driven studies to identify prognostic TSCC biomarkers. Although fundamentally prognostic, we discussed their theoretical translational relevance regarding future clinical decisions—such as treatment stratification or surveillance intensity—while strictly framing them as preliminary, hypothesis-generating targets. PubMed, Scopus, Web of Science, and Cochrane were searched for original human studies published between 2014 and 2024 using high-throughput genomic or transcriptomic profiling. Study selection followed referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), data were extracted with a structured workbook, and risk of bias was assessed using QUIPS and PROBAST, with reporting completeness appraised using REMARK. Seventeen studies were included, identifying 85 distinct biomarkers. Across biomarkers supported by multivariable overall survival analyses, higher-risk associations were reported for NELL2, PDE4D, CTTN, HBEGF, and CA9, whereas lower-risk associations were reported for AC139530.1, LINC01711, CCDC96, CYP2J2, and SPAG16. Recurrent biological themes included IL-17 signaling, ECM-receptor interaction, and focal adhesion. CA9 was the only biomarker reported in more than one included study, supporting its prioritization for validation. Although the evidence remains heterogeneous and largely hypothesis-generating, these markers may support the future validation of response-oriented therapeutic stratification in TSCC. Full article
(This article belongs to the Special Issue Molecular Markers of Tumor Response and Toxicity of Antitumor Therapy)
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22 pages, 383 KB  
Review
Molecular Mechanisms of Radioiodine Refractoriness in Differentiated Thyroid Cancer: Focus on Sodium/Iodide Symporter Dysregulation
by Vladimir D. Rokashkov, Liudmila V. Spirina, Natalya V. Tarasenko and Svetlana Yu. Chizhevskaya
Curr. Issues Mol. Biol. 2026, 48(4), 362; https://doi.org/10.3390/cimb48040362 - 31 Mar 2026
Cited by 1 | Viewed by 1811
Abstract
The sodium/iodide symporter (NIS/SLC5A5) is a major determinant of radioiodine therapy efficacy in differentiated thyroid cancer (DTC). This narrative review examines the molecular mechanisms underlying NIS dysregulation and radioiodine refractoriness in DTC. Reduced NIS expression or function in radioiodine-refractory DTC is associated with [...] Read more.
The sodium/iodide symporter (NIS/SLC5A5) is a major determinant of radioiodine therapy efficacy in differentiated thyroid cancer (DTC). This narrative review examines the molecular mechanisms underlying NIS dysregulation and radioiodine refractoriness in DTC. Reduced NIS expression or function in radioiodine-refractory DTC is associated with multiple mechanisms, including transcriptional suppression linked to MAPK/ERK and PI3K/AKT pathway activation and disruption of thyroid differentiation programs; epigenetic silencing involving SLC5A5 regulatory regions; impaired protein trafficking and membrane localization; and post-transcriptional regulation by microRNAs such as miR-221-3p, miR-222-3p, miR-146b-3p, and miR-204-5p. Genetic alterations including BRAF V600E and TERT promoter mutations are associated with dedifferentiated tumor phenotypes and poor radioiodine response. Redifferentiation approaches using MAPK pathway inhibitors such as selumetinib and dabrafenib can restore iodine uptake in selected patients, although the overall clinical applicability of these strategies remains under evaluation. A better understanding of these mechanisms may support improved biologic stratification and more selective therapeutic decision-making in radioiodine-refractory DTC. Full article
(This article belongs to the Special Issue Molecular Markers of Tumor Response and Toxicity of Antitumor Therapy)
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