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Molecular Insights into Cancer Biomarkers: Identification and Practical Applications

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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 June 2026 | Viewed by 14883

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Special Issue Editor

Dr. Mihaela Chivu-Economescu

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Guest Editor

Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania
Interests: immunology and immune response during viral infections; oncology; immunotherapy; intracellular signalling; targeted therapy
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Special Issue Information

Dear Colleagues,

Nowadays, cancer research is evolving, and the identification of new biomarkers that can provide early cancer detection, predict its progression, or assist in treatment monitoring—preferably in a non-invasive manner—is transforming the oncology field in terms of diagnosis, prognosis, and treatment strategies. This Special Issue will focus on the discovery, validation, and clinical application of cancer biomarkers, with an emphasis on their role in tumor growth, progression, metastasis, and therapeutic intervention. This issue aims to highlight cutting-edge research on the identification of novel cancer biomarkers and their roles in tumor progression and metastasis, tissue matrix remodeling proteins and their significance in cancer metastasis, and biomarker-based therapeutic strategies. Also, a special emphasis will be placed on liquid biopsy biomarkers, with applications for monitoring tumor dynamics and therapeutic response.

This Special Issue should appeal to a broad audience of oncologists, molecular biologists, and translational researchers, driving forward the integration of biomarkers into precision oncology.

Dr. Mihaela Chivu-Economescu
Guest Editor

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Keywords

cancer biomarkers
liquid biopsy
early detection
progression
prognosis
treatment monitoring

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Published Papers (7 papers)

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Research

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17 pages, 2295 KB

Open AccessArticle

The Hippo Pathway in Metaplastic Breast Carcinoma: Prognostic Significance and Therapeutic Implications

by Eleni Papamattheou, Alkistis Papatheodoridi, Ioannis Katsaros, Garyfalia Bletsa, Afroditi Nonni, Constantine Dimitrakakis, Dimitrios Haidopoulos, Angeliki Andrikopoulou, Areti Papakosta, Spyridon Marinopoulos, Aris Giannos, Sofia Koura, Eftychia Papachatzopoulou, Ioannis K. Papapanagiotou, Georgios I. Metaxas, Aikaterini-Gavriela Giannakaki, Meletios-Athanasios Dimopoulos and Flora Zagouri

Curr. Issues Mol. Biol. 2025, 47(12), 1060; https://doi.org/10.3390/cimb47121060 - 18 Dec 2025

Viewed by 541

Abstract

Background/objectives: Metaplastic breast carcinoma (MpBC) is a rare, poorly differentiated breast cancer defined by the presence of ductal carcinoma along with areas of matrix-producing, spindle-cell, sarcomatous, or squamous differentiation. It does not express hormone receptors and has a poor overall prognosis. The Hippo molecular pathway was recently related to cancer progression and adjuvant therapy resistance. The objective of this study was to evaluate the expression of Hippo pathway transducers, YAP/TAZ, CCND1, and CTGF, in MpBC and their relation to the clinicopathological characteristics of the disease. Methods: Specimens from patients with MpBC treated at our department from 2003 to 2021 were analyzed utilizing immunohistochemistry and real-time PCR. Results: Forty-four female patients (62.6 ± 14.7 years old) met inclusion criteria and were included in this study. Strong nuclear YAP/TAZ expression was found in 61.4% of patients, while the expressions of CCND1 and CTGF were 3.9% and 12.5%, respectively. Patients presenting at an advanced stage had a statistically worse prognosis compared to the ones diagnosed with stage IA disease. Adjuvant chemotherapy was associated with better overall survival, while disease recurrence was significantly associated with a worse prognosis. Conclusions: Advanced stage at diagnosis and disease recurrence were significantly associated with worse prognosis in MpBC. However, adjuvant chemotherapy significantly led to better overall survival. The Hippo pathway is frequently deregulated (nuclear YAP/TAZ in 61.4% of patients), suggesting it is a compelling novel therapeutic target for this aggressive disease. Full article

(This article belongs to the Special Issue Molecular Insights into Cancer Biomarkers: Identification and Practical Applications)

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12 pages, 302 KB

Open AccessArticle

Potential Resistance to Oxaliplatin-Based Regimens in Gastric Cancer Patients with ERBB2 R678Q Mutation: Evidence from a National Genomic Database

by Shuhei Suzuki, Manabu Seino, Hidenori Sato, Yosuke Saito, Koki Saito, Yuta Yamada, Koshi Takahashi, Ryosuke Kumanishi and Tadahisa Fukui

Curr. Issues Mol. Biol. 2025, 47(6), 430; https://doi.org/10.3390/cimb47060430 - 6 Jun 2025

Cited by 3 | Viewed by 1668

Abstract

Epidermal growth factor receptor 2 (ERBB2/HER2) is a critical biomarker in gastric cancer management, but the clinical implications of specific ERBB2 mutations remain poorly characterized. Methods/Results: We investigated the ERBB2 R678Q mutation, utilizing the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which involved the analysis of 3116 gastric/gastroesophageal junction adenocarcinomas. ERBB2 mutations were identified in 130 cases, with R678Q present in 40 patients. These patients exhibited significantly lower response rates to oxaliplatin-based regimens compared to ERBB2 wild-type cases (19.0% vs. 38.0%, p = 0.03), while other ERBB2 mutations demonstrated no such resistance. No significant differences in the response were observed to the ramucirumab or nivolumab regimens. Conclusions: Our findings suggest that the ERBB2 R678Q mutation may predict a poor response to oxaliplatin-based therapy. This study provides real-world evidence supporting the potential clinical relevance of this specific ERBB2 mutation in treatment decision making for gastric cancer. Full article

(This article belongs to the Special Issue Molecular Insights into Cancer Biomarkers: Identification and Practical Applications)

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11 pages, 1260 KB

Open AccessArticle

Circulating Tumor Cells in Head and Neck Squamous-Cell Carcinoma Exhibit Distinct Properties Based on Targeted Epithelial-Related Markers

by Kazuaki Chikamatsu, Hideyuki Takahashi, Hiroe Tada, Miho Uchida, Shota Ida, Yuichi Tomidokoro and Masaomi Motegi

Curr. Issues Mol. Biol. 2025, 47(4), 240; https://doi.org/10.3390/cimb47040240 - 29 Mar 2025

Cited by 6 | Viewed by 1548

Abstract

The detection of circulating tumor cells (CTCs) using immunoaffinity-based methods often relies on epithelial-related markers, which may bias the selection of CTCs and limit the biological information obtained, depending on the targeted antigens. Herein, we compared the molecular profiles and clinical significance of CTCs based on the expression of epithelial-related markers (EPCAM, EGFR, and MET) in patients with head and neck squamous-cell carcinoma (HNSCC). CTCs were detected using density gradient separation and CD45-negative selection, followed by quantitative PCR for epithelial-related marker expression. Expression profiles of epithelial–mesenchymal transition (EMT)-related (VIM, CDH1, CDH2, SNAI1, ZEB1, ZEB2, and TWIST1) and immune-regulatory (CD274 and PDCD1LG2) genes were compared. Moreover, the association between marker expression and clinical factors was analyzed. Among the 60 patients with CTCs, 48 (80.0%), 20 (33.3%), and 31 (51.7%) were positive for EPCAM, EGFR, and MET, respectively. A significant correlation was observed between CTCs expressing EPCAM and EGFR. CTCs expressing distinct markers showed differing EMT-related and immune-regulatory gene expression. EPCAM+ CTCs were associated with advanced-stage disease, while EGFR+ CTCs were correlated with locoregional relapse and shorter progression-free survival (p = 0.007; hazard ratio = 3.254). Patients with EPCAM/EGFR double-positive CTCs had the poorest prognosis. These findings emphasize the importance of marker selection in liquid biopsy technologies and highlight the need for improved detection methods and the further investigation of CTC biology. Full article

(This article belongs to the Special Issue Molecular Insights into Cancer Biomarkers: Identification and Practical Applications)

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Review

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35 pages, 1919 KB

Open AccessReview

Precision Oncology in Ocular Melanoma: Integrating Molecular and Liquid Biopsy Biomarkers

by Snježana Kaštelan, Fanka Gilevska, Zora Tomić, Josipa Živko and Tamara Nikuševa-Martić

Curr. Issues Mol. Biol. 2026, 48(2), 131; https://doi.org/10.3390/cimb48020131 - 25 Jan 2026

Cited by 1 | Viewed by 922

Abstract

Ocular melanomas, comprising uveal melanoma (UM) and conjunctival melanoma (CoM), represent the most common primary intraocular and ocular surface malignancies in adults. Although rare compared with cutaneous melanoma, they exhibit unique molecular landscapes that provide critical opportunities for biomarker-driven precision medicine. In UM, recurrent mutations in GNAQ and GNA11, together with alterations in BAP1, SF3B1, and EIF1AX, have emerged as key prognostic biomarkers that stratify metastatic risk and guide surveillance strategies. Conversely, in CoM, the mutational spectrum overlaps with cutaneous melanoma, with frequent alterations in BRAF, NRAS, NF1, and KIT, offering actionable targets for personalised treatment. Beyond genomics, epigenetic signatures, microRNAs, and protein-based markers provide further insights into tumour progression, microenvironmental remodelling, and immune evasion. In parallel, liquid biopsy has emerged as a minimally invasive approach for real-time disease monitoring. Analyses of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and exosome-derived microRNAs demonstrate increasing potential for early detection of minimal residual disease, prognostic assessment, and evaluation of treatment response. However, the clinical integration of these biomarkers remains limited by tumour heterogeneity, technical variability, and the lack of unified translational frameworks. This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management. Full article

(This article belongs to the Special Issue Molecular Insights into Cancer Biomarkers: Identification and Practical Applications)

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19 pages, 574 KB

Open AccessReview

Bridging Andrology and Oncology: Prognostic Indicators of Cancer Among Infertile Men

by Athanasios Zachariou, Efthalia Moustakli, Athanasios Zikopoulos, Maria Filiponi, Anastasios Potiris, Nikolaos Kathopoulis, Themos Grigoriadis, Maria Tzeli, Nikolaos Machairiotis, Ekaterini Domali, Nikolaos Thomakos and Sofoklis Stavros

Curr. Issues Mol. Biol. 2025, 47(11), 930; https://doi.org/10.3390/cimb47110930 - 8 Nov 2025

Cited by 1 | Viewed by 1387

Abstract

Approximately 7% of males globally suffer from male infertility, which is becoming more widely acknowledged as a clinical indicator of potential health hazards as well as a cause of reproductive failure. Among these, cancer has become a significant worry due to mounting evidence that spermatogenesis impairment is associated with increased risk of prostate, testicular, and other cancers. Male infertility may be an early clinical manifestation of systemic genomic instability due to shared biological pathways, such as Y-chromosome microdeletions (AZF regions), germline DNA repair defects, mutations in tumor suppressor genes (e.g., BRCA1/2, TP53), mismatch repair gene mutations (e.g., MLH1, MSH2), and dysregulated epigenetic profiles. This narrative review covers the most recent research on prognostic markers of cancer in infertile men. These include molecular biomarkers such as genetic, epigenetic, and proteomic signatures; endocrine and hormonal profiles; and clinical predictors such as azoospermia, severe oligozoospermia, and a history of cryptorchidism. The possibility of incorporating these indicators into risk stratification models for precision medicine and early cancer surveillance is highlighted. For this high-risk group, bridging the domains of andrology and oncology may allow for better counseling, earlier detection, and focused therapies. Full article

(This article belongs to the Special Issue Molecular Insights into Cancer Biomarkers: Identification and Practical Applications)

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20 pages, 937 KB

Open AccessReview

Multi-Biofluid Approaches for cftDNA and cftRNA Biomarker Detection: Advances in Early Cancer Detection and Monitoring

by Douglas M. Ruden

Curr. Issues Mol. Biol. 2025, 47(9), 738; https://doi.org/10.3390/cimb47090738 - 10 Sep 2025

Cited by 1 | Viewed by 2290

Abstract

Cell-free tumor DNA (cftDNA) and cell-free tumor RNA (cftRNA) are emerging as powerful biomarkers for cancer detection, monitoring, and prognosis. These nucleic acids, released into the bloodstream by tumor cells, carry cancer-specific genetic and epigenetic alterations and can be detected non-invasively. Detection before clinical diagnosis offers a unique opportunity for earlier intervention yet requires longitudinal cohort studies to establish pre-diagnostic biomarker profiles. Current technologies enable sensitive quantification of cftDNA and cftRNA, with spike-in controls allowing for absolute quantification of single nucleosome-bound cftDNA, addressing a key limitation in liquid biopsy assays. Advances, such as DNA-PAINT, now permit single-molecule resolution detection of point mutations and methylation patterns characteristic of cancer, while new proteomics methods can identify the tissue of origin of exosome-derived nucleic acid. This review discusses the state-of-the-art detection strategies for cftDNA and cftRNA, highlights the gaps in longitudinal sampling, and outlines future research directions toward integrating multiomic liquid biopsy approaches for improved early diagnosis, monitoring, and relapse detection. Full article

(This article belongs to the Special Issue Molecular Insights into Cancer Biomarkers: Identification and Practical Applications)

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15 pages, 2011 KB

Open AccessReview

Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy

by Laura Denisa Dragu, Mihaela Chivu-Economescu, Ioana Madalina Pitica, Lilia Matei, Coralia Bleotu, Carmen Cristina Diaconu and Laura Georgiana Necula

Curr. Issues Mol. Biol. 2025, 47(7), 525; https://doi.org/10.3390/cimb47070525 - 8 Jul 2025

Cited by 5 | Viewed by 5732

Abstract

This manuscript assesses the critical role of exosomal PD-L1 (ExoPD-L1) in immune suppression, tumor progression, and resistance to therapy. ExoPD-L1 has been identified as a key mediator of tumor immune evasion, contributing to systemic immunosuppression beyond the tumor microenvironment (TME) due to its capacity to travel to distant anatomical sites. In this context, the review aims to elaborate on the mechanisms by which exosomal PD-L1 interacts with T cell receptors and modulates both the tumor microenvironment and immune responses, impacting patient outcomes. We further explore emerging therapeutic strategies that target ExoPD-L1 to enhance the effectiveness of immunotherapy. Blocking ExoPD-L1 offers a novel approach to counteracting immune escape in cancer. Promising strategies include inhibiting exosome biogenesis with GW4869 or Rab inhibitors, neutralizing ExoPD-L1 with targeted antibodies, and silencing PD-L1 expression through RNA interference (RNAi) or CRISPR-based methods. While each approach presents certain limitations, their integration into combination therapies holds significant potential to improve the efficacy of immune checkpoint inhibitors. Future research should focus on optimizing these strategies for clinical application, with particular attention to improving delivery specificity and minimizing off-target effects. Full article

(This article belongs to the Special Issue Molecular Insights into Cancer Biomarkers: Identification and Practical Applications)

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