ijms-logo

Journal Browser

Journal Browser

Molecular Biology of Cancer—Implications for Diagnosis and Treatment: 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 3882

Special Issue Editors


E-Mail Website
Guest Editor
Faculty of Engineering and Science, University of Greenwich London, Chatham Maritime ME4 4TB, UK
Interests: cholinergic neuron diseases; Alzheimer’s and Dementia; neuron
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King's College London, London SE1 9RT, UK
2. Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent ME7 5NY, UK
3. Kent Medway Medical School, University of Kent, Canterbury, Kent CT2 7LX, UK
4. AELIA Organization, 9th Km Thessaloniki—Thermi, 57001 Thessaloniki, Greece
Interests: prostate cancer; renal cancer; ovarian cancer; homologous recombination of DNA; PARP inhibitors; cervical cancer; carcinoma of unknown primary; colorectal cancer; cancer and autoimmune diseases; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer has a genetic background. The expression of oncogenesis is an important event in the early stages of tumor formation. Most common cancers are caused by acquired mutations in somatic cells, whilst specific germline mutations account for rare hereditary cancer syndromes. Among the cancer-associated genes, oncogenes undergo activation and are phenotypically dominant, whereas tumor suppressor genes undergo inactivation and are phenotypically recessive. The biological behavior of cancer can be considered in terms of eight specific hallmarks and two additional so-called enabling characteristics. The improvement of our knowledge regarding the molecular mechanisms implicated in cancer progression, via the identification of the pathways that influence cancer therapy, is an ongoing endeavor. Via the application of cutting-edge technologies, including genomics, computational biology, tumor imaging, and in vitro and in vivo functional models, it has become feasible to identify the genes involved in the development of cancer. Furthermore, advances in genomics technology facilitating the routine DNA and RNA sequencing of tumors, the single-cell transcriptomic profiling of cancer cells, and whole-genome CRISPR screens have contributed to the growing success of oncology–precision-medicine-targeted therapies directed against tumors and components of the tumor microenvironment.

Through this Special Issue, we aim to shed light on novel molecular diagnostic technologies and novel therapeutic approaches that are based on recent advances in cancer biology and molecular genetics.

We welcome the submission of original articles, reviews, and communications by experts in this field. This Special Issue is supervised by Prof. Dr. Stergios Boussios, Prof. Dr. Saak Victor Ovsepian, and Prof. Dr. Matin Sheriff, and assisted by our Topical Advisory Panel Member Dr. Tania Vanessa Pierfelice (University “G. d’Annunzio” of Chieti-Pescara).

Volume I of the Special IssueMolecular Biology of Cancer—Implications for Diagnosis and Treatment
Volume II of the Special IssueMolecular Biology of Cancer—Implications for Diagnosis and Treatment: 2nd Edition”

Prof. Dr. Saak Victor Ovsepian
Prof. Dr. Stergios Boussios
Prof. Dr. Matin Sheriff
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 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • genomics
  • epigenetics
  • translational research
  • oncology precision medicine

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Related Special Issues

Published Papers (7 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 5218 KiB  
Article
Mechanistic Insights into Radiation Resistance in Colorectal Cancer: Gene Exploration Study
by Beamjun Park, Soohyeon Lee, Inyoung Jo, Donghyun Kang, Taewan Kim, Jaesung Ryu, Hyejeong Kong, Moojun Baek and Taesung Ahn
Int. J. Mol. Sci. 2025, 26(8), 3849; https://doi.org/10.3390/ijms26083849 - 18 Apr 2025
Viewed by 68
Abstract
Radiotherapy is a cornerstone of colorectal cancer (CRC) treatment; however, its therapeutic efficacy is often compromised by both intrinsic and acquired resistance in CRC cells. This study employed small interfering RNA (siRNA) technology to elucidate the functional roles of BAMBI, GADD34, NFKBIA, and [...] Read more.
Radiotherapy is a cornerstone of colorectal cancer (CRC) treatment; however, its therapeutic efficacy is often compromised by both intrinsic and acquired resistance in CRC cells. This study employed small interfering RNA (siRNA) technology to elucidate the functional roles of BAMBI, GADD34, NFKBIA, and NFKBID in CRC cell lines SW480 and HCT116. We assessed their impact on key cellular processes and radiation sensitivity. Gene silencing of all four target genes significantly suppressed CRC cell proliferation, migration, and invasion. Moreover, siRNA-mediated knockdown enhanced radiation sensitivity, as evidenced by a substantial increase in apoptosis and a marked reduction in cell viability compared with controls. These findings suggest that BAMBI, GADD34, NFKBIA, and NFKBID serve as critical regulators of CRC progression and radiation resistance. Overall, this study provides a mechanistic foundation for further exploration into the pathways underlying radiation resistance and underscores the potential for developing personalized radiotherapy strategies guided by molecular profiling. Full article
Show Figures

Figure 1

21 pages, 4777 KiB  
Article
Lapatinib-Resistant HER2+ Breast Cancer Cells Are Associated with Dysregulation of MAPK and p70S6K/PDCD4 Pathways and Calcium Management, Influence of Cryptotanshinone
by Jorge Hernández-Valencia, Ruth García-Villarreal, Manuel Rodríguez-Jiménez, Alex Daniel Hernández-Avalos, Ignacio A. Rivero, José Luis Vique-Sánchez, Brenda Chimal-Vega, Angel Pulido-Capiz and Victor García-González
Int. J. Mol. Sci. 2025, 26(8), 3763; https://doi.org/10.3390/ijms26083763 - 16 Apr 2025
Viewed by 236
Abstract
Resistance to HER2 tyrosine-kinase inhibitor Lapatinib (Lap) is one of the leading causes of cancer treatment failure in HER2+ breast cancer (BC), associated with an aggressive tumor phenotype. Cryptotanshinone (Cry) is a natural terpene molecule that could function as a chemosensitizer by disturbing [...] Read more.
Resistance to HER2 tyrosine-kinase inhibitor Lapatinib (Lap) is one of the leading causes of cancer treatment failure in HER2+ breast cancer (BC), associated with an aggressive tumor phenotype. Cryptotanshinone (Cry) is a natural terpene molecule that could function as a chemosensitizer by disturbing estrogen receptor (ERα) signaling and inhibiting the protein translation factor-4A, eIF4A. Therefore, we evaluated Cry dual regulation on eIF4A and ERα. This study aimed to elucidate the underlying mechanisms of Lap chemoresistance and the impact of Cry on them. We generated two Lap-resistant BT474 cell HER2+ variants named BT474LapRV1 and BT474LapRV2 with high chemoresistance levels, with 7- and 11-fold increases in EC50, respectively, compared to BT474 parental cells. We found a PDCD4-p70S6Kβ axis association with Lap chemoresistance. However, a concomitant down-regulation of the RAF-MEK-ERK cell survival pathway and NF-κB was found in the chemoresistant cell variants; this phenomenon was exacerbated by joint treatment of Cry and Lap under a Lap plasmatic reported concentration. Optimized calcium management was identified as a compensatory mechanism contributing to chemoresistance, as determined by the higher expression of calcium pumps PMCA1/4 and SERCA2. Contrary to expectations, a combination of Lap and Cry did not affect the chemoresistance despite the ERα down-regulation; Cry-eIF4A binding possibly dampens this condition. Results indicated the pro-survival eIF4A/STAT/Bcl-xl pathway and that the down-regulation of the MAPK-NF-κB might function as an adaptive mechanism; this response may be compensated by calcium homeostasis in chemoresistance, highlighting new adaptations in HER2+ cells that lead to chemoresistance. Full article
Show Figures

Graphical abstract

13 pages, 7845 KiB  
Article
Diagnostic Potential of CD44, CD133, and VDR in Epithelial Ovarian Tumors: Association with Histopathology Parameters
by Ljubiša Jovanović, Branka Šošić-Jurjević, Anđa Ćirković, Sandra Dragičević, Branko Filipović, Svetlana Milenković, Stefan Dugalić, Miroslava Gojnić-Dugalić and Aleksandra Nikolić
Int. J. Mol. Sci. 2025, 26(8), 3729; https://doi.org/10.3390/ijms26083729 - 15 Apr 2025
Viewed by 185
Abstract
Cancer stem cells (CSCs) significantly contribute to heterogeneity, malignancy, and therapy resistance in ovarian cancer. Recent studies emphasize the role of the vitamin D receptor (VDR) in regulating cell differentiation and stemness in various types of cancer. This study aims to determine the [...] Read more.
Cancer stem cells (CSCs) significantly contribute to heterogeneity, malignancy, and therapy resistance in ovarian cancer. Recent studies emphasize the role of the vitamin D receptor (VDR) in regulating cell differentiation and stemness in various types of cancer. This study aims to determine the expression levels of CD44, CD133, and VDR in epithelial ovarian tumors (EOTs) and to compare these levels across different tumor types, including benign, atypical proliferative tumors, and five types of malignant phenotypes, in order to evaluate their potential as diagnostic tools for malignancy. Tissue samples from 218 patients diagnosed with EOT were analyzed. Clinical and histopathologic parameters were recorded. Quantitative immunohistochemical tissue microarray analysis was used to assess the expression levels of CD44, CD133, and VDR using two different scoring systems. Comparisons were made between benign tumors (n = 45), atypical proliferative tumors (n = 42), and ovarian carcinomas (n = 131), including high-grade serous (HGSC) and non-HGSC subtypes. Ovarian cancer, especially HGSC, showed a significantly higher expression of CD44 and VDR (p < 0.05) compared to atypical proliferative tumors and benign tumors. The expression of CD133 was highest in atypical proliferative tumors (p < 0.05). A moderate positive correlation was found between CD44, CD133, and VDR in all groups, with significant correlations with tumor grade and FIGO stage in ovarian cancer (p < 0.05). The increased expression of CD44 and VDR in aggressive ovarian cancer, along with elevated CD133 levels in atypical proliferative tumors, highlights the complexity of tumor biology. These markers may serve as valuable targets for the diagnosis of ovarian cancer. Full article
Show Figures

Figure 1

22 pages, 3375 KiB  
Article
Synergistic HDAC4/8 Inhibition Sensitizes Osteosarcoma to Doxorubicin via pAKT/RUNX2 Pathway Modulation
by Anuja Gajanan Magar, Vivek Kumar Morya, Young-Ho Koh and Kyu-Cheol Noh
Int. J. Mol. Sci. 2025, 26(8), 3574; https://doi.org/10.3390/ijms26083574 - 10 Apr 2025
Viewed by 181
Abstract
Osteosarcoma is a highly aggressive bone malignancy, particularly challenging in metastatic cases, with a 5-year survival rate remaining under 30%. Although doxorubicin (doxo) is a standard first-line chemotherapeutic agent, its clinical utility is often hindered by the development of drug resistance and associated [...] Read more.
Osteosarcoma is a highly aggressive bone malignancy, particularly challenging in metastatic cases, with a 5-year survival rate remaining under 30%. Although doxorubicin (doxo) is a standard first-line chemotherapeutic agent, its clinical utility is often hindered by the development of drug resistance and associated systemic toxicity. Emerging evidence highlights the role of epigenetic alterations, particularly those involving histone deacetylases (HDACs), in promoting chemoresistance. In this context, the present study aimed to evaluate the therapeutic potential of combining doxo with the selective HDAC inhibitors, tasquinimod (Tas, targeting HDAC4) and PCI-34051 (PCI, targeting HDAC8), in SJSA-1 osteosarcoma cells. Utilizing both 2D and 3D in vitro models, the combination treatment (referred to as the T4 group) significantly reduced cell viability by 57.69% in 2D cultures and decreased spheroid volume by 35.19% in 3D models. The apoptotic response was markedly enhanced, with late apoptosis reaching 64.59% and necrosis at 32.07%, both surpassing the effects observed with doxo alone. Furthermore, wound healing assays demonstrated a 37.74% inhibition of migration, accompanied by a decreased expression of the matrix metalloproteinases MMP9 and MMP13. Mechanistically, the combination therapy led to the downregulation of protein kinase B (pAKT) and RUNX2, along with upregulation of apoptotic markers, including caspase 8, caspase 3, and cleaved caspase 3, indicating a disruption of key survival pathways. These findings suggest that dual HDAC inhibition with Tas and PCI can potentiate doxo efficacy by enhancing apoptosis, inhibiting proliferation, and reducing metastatic potential, thus offering a promising strategy to overcome chemoresistance in osteosarcoma. Further preclinical and clinical studies are required to validate these therapeutic benefits. Full article
Show Figures

Graphical abstract

15 pages, 3437 KiB  
Article
Dysbiosis of Bile Microbiota in Cholangiocarcinoma Patients: A Comparison with Benign Biliary Diseases
by Wonsuk Park, Sang Kuon Lee, Jin Gwack, Seung Yeob Lee, Yong Gon Cho, Sang-Bum Kang and Joonhong Park
Int. J. Mol. Sci. 2025, 26(4), 1577; https://doi.org/10.3390/ijms26041577 - 13 Feb 2025
Viewed by 601
Abstract
Dysbiosis in the bile microbiota of cholangiocarcinoma (CCA) patients suggests a potential role for microbial alterations in the pathogenesis of CCA. This study aimed to investigate bile microbial communities in patients with CCA and compare them to those in individuals with benign biliary [...] Read more.
Dysbiosis in the bile microbiota of cholangiocarcinoma (CCA) patients suggests a potential role for microbial alterations in the pathogenesis of CCA. This study aimed to investigate bile microbial communities in patients with CCA and compare them to those in individuals with benign biliary diseases as a control (CTR) group. Microbial profiling was conducted using next-generation sequencing (NGS), targeting the V3–V4 regions of the 16S rRNA gene, followed by bioinformatics analysis using the VSEARCH and EzBioCloud platforms. Alpha and beta diversity analyses were performed to assess microbial richness and structural differences. The linear discriminant analysis effect size (LEfSe) was utilized to identify potential microbial biomarkers. Results: This study identified distinct microbial profiles in the two groups at both the phylum and genus levels. In the CTR group, Pseudomonadota (65%) was the dominant phyla, while Bacillota (49%) was more abundant in the CCA group. At the genus level, Escherichia (29%), Enterobacteriaceae (12%), Enterococcus (8%), Ralstonia (8%), and Clostridium (5%) were more prevalent in the CTR group, whereas Streptococcus (34%), Ralstonia (8%), and Veillonella (5%) were dominant in the CCA group. Although an alpha diversity analysis showed no statistically significant differences in species richness or diversity between groups, a beta diversity analysis revealed significant structural differences associated with disease severity. Our comparative microbiome study using LEfSe analysis suggested a statistically significant inhibition of normal intestinal bacterial flora in patients with CCA who had not received any treatment. These findings suggest that microbial dysbiosis may play a role in the pathogenesis of CCA. Specific microbial taxa were identified as potential biomarkers for distinguishing benign from malignant diseases. These results underscore the potential role of microbial dysbiosis in CCA pathogenesis and highlight the bile microbiota’s utility as a diagnostic marker for biliary diseases. Full article
Show Figures

Figure 1

Review

Jump to: Research

13 pages, 1077 KiB  
Review
Pertuzumab in Combination with Trastuzumab and Docetaxel as Adjuvant Doublet Therapy for HER2-Positive Breast Cancer: A Systematic Review
by Ignacio Ventura, Nerea Pinilla Salcedo, Marcelino Pérez-Bermejo, Javier Pérez-Murillo, Manuel Tejeda-Adell, Francisco Tomás-Aguirre, María Ester Legidos-García and María Teresa Murillo-Llorente
Int. J. Mol. Sci. 2025, 26(5), 1908; https://doi.org/10.3390/ijms26051908 - 23 Feb 2025
Viewed by 760
Abstract
Breast cancer is the most clinically relevant pathology of the mammary gland and is currently the most diagnosed malignant disease among women worldwide. In breast cancer prevention, it is important to consider that the risk of developing the disease is not the same [...] Read more.
Breast cancer is the most clinically relevant pathology of the mammary gland and is currently the most diagnosed malignant disease among women worldwide. In breast cancer prevention, it is important to consider that the risk of developing the disease is not the same for the entire population. This pathology presents heterogeneous clinical manifestations and the most common classification is related to the following hormonal receptors: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and triple-negative (TNBC). Currently, a new class of therapy is being used for cancer treatment: anti-body-drug conjugates. A bibliographic search was performed by establishing keywords and then combining them using Boolean operators OR and AND. Thus, the search equation was formulated according to the PICO search question to be used in the PubMed database. Results: Fifteen studies that met the established inclusion criteria were analyzed, and their methodological quality was assessed using the Joanna Briggs Institute approach, demonstrating high reliability in the results obtained, the analyzed studies focus on the combination of adjuvant Pertuzumab + Trastuzumab with chemotherapy for the treatment of HER2-positive breast cancer. Scientific evidence suggests that the combination of pertuzumab and trastuzumab not only improves the survival of patients with HER2-positive breast cancer but also provides a safe and flexible treatment option. Full article
Show Figures

Figure 1

15 pages, 1057 KiB  
Review
Exploring the Therapeutic Potential of BRCA1 and BRCA2 as Targets in Canine Oncology: A Comprehensive Review of Their Role in Cancer Development and Treatment
by Jayson Cagadas Pasaol, Agnieszka Śmieszek and Aleksandra Pawlak
Int. J. Mol. Sci. 2025, 26(4), 1768; https://doi.org/10.3390/ijms26041768 - 19 Feb 2025
Viewed by 1069
Abstract
Tumor diseases represent a significant global health challenge, impacting both humans and companion animals, notably dogs. The parallels observed in the pathophysiology of cancer between humans and dogs underscore the importance of advancing comparative oncology and translational research methodologies. Furthermore, dogs serve as [...] Read more.
Tumor diseases represent a significant global health challenge, impacting both humans and companion animals, notably dogs. The parallels observed in the pathophysiology of cancer between humans and dogs underscore the importance of advancing comparative oncology and translational research methodologies. Furthermore, dogs serve as valuable models for human cancer research due to shared environments, genetics, and treatment responses. In particular, breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2), which are critical in human cancer, also influence the development and progression of canine tumors. The role of BRCA1 and BRCA2 in canine cancers remains underexplored, but its potential significance as therapeutic targets is strongly considered. This systematic review aims to broaden the discussion of BRCA1 and BRCA2 beyond mammary tumors, exploring their implications in various canine cancers. By emphasizing the shared genetic underpinnings between species and advocating for a comparative approach, the review indicates the potential of BRCA genes as targets for innovative cancer therapies in dogs, contributing to advances in human and veterinary oncology. Full article
Show Figures

Figure 1

Back to TopTop