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Molecular Biology of Cancer—Implications for Diagnosis and Treatment 2.0

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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: 5 December 2024 | Viewed by 8781

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Special Issue Editors

Prof. Dr. Matin Sheriff

E-Mail Website
Guest Editor

Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham ME7 5NY, Kent, UK
Interests: prostate cancer; bladder cancer; renal cancer; DNA mismatch repair
Special Issues, Collections and Topics in MDPI journals

Dr. Stergios Boussios

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, Kent, Gillingham ME7 5NY, UK
3. Kent Medway Medical School, University of Kent, Kent , Canterbury CT2 7LX, UK
4. AELIA Organization, 9(th)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.

The Volume I of the Special Issue "Molecular Biology of Cancer—Implications for Diagnosis and Treatment".

Prof. Dr. Matin Sheriff
Dr. Stergios Boussios
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

Published Papers (5 papers)

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Research

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17 pages, 3917 KiB

Open AccessArticle

Prognostic Value of HHLA2 in Patients with Solid Tumors: A Meta-Analysis

by Agnieszka Kula, Miriam Dawidowicz, Sylwia Mielcarska, Elżbieta Świętochowska and Dariusz Waniczek

Int. J. Mol. Sci. 2024, 25(9), 4760; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25094760 - 26 Apr 2024

Viewed by 308

Abstract

HHLA2 is a checkpoint from the B7 family that can play a co-stimulatory or co-inhibitory role in cancer, depending on the binding receptor. The aim of this meta-analysis was to assess the relationship between HHLA2 levels and its impact on the prognosis of patients with solid cancers. The study used data from PubMed, Embase, Web of Science (WOS), Cochrane and SCOPUS databases. The R studio software was used for the data analysis. The study assessed overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) by pooling appropriate hazard ratios (HR). Eighteen studies (2880 patients’ data) were included. High expression of HHLA2 was associated with worse OS (HR = 1.58, 95% CI: 1.23–2.03), shorter RFS (HR = 1.95, 95% CI: 1.38–2.77) and worse DFS (HR = 1.45, 95% CI: 1.01–2.09) in patients with solid cancers. The current study suggests that high expression of HHLA2 is associated with poorer prognosis in patients with solid cancers. Full article

(This article belongs to the Special Issue Molecular Biology of Cancer—Implications for Diagnosis and Treatment 2.0)

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16 pages, 7244 KiB

Open AccessArticle

Lung Cancer Cell-Derived Exosome Detection Using Electrochemical Approach towards Early Cancer Screening

by Koosha Irani, Hossein Siampour, Abdollah Allahverdi, Ahmad Moshaii and Hossein Naderi-Manesh

Int. J. Mol. Sci. 2023, 24(24), 17225; https://doi.org/10.3390/ijms242417225 - 7 Dec 2023

Viewed by 1205

Abstract

Lung cancer is one of the deadliest cancers worldwide due to the inability of existing methods for early diagnosis. Tumor-derived exosomes are nano-scale vesicles released from tumor cells to the extracellular environment, and their investigation can be very useful in both biomarkers for early cancer screening and treatment assessment. This research detected the exosomes via an ultrasensitive electrochemical biosensor containing gold nano-islands (Au-NIs) structures. This way, a high surface-area-to-volume ratio of nanostructures was embellished on the FTO electrodes to increase the chance of immobilizing the CD-151 antibody. In this way, a layer of gold was first deposited on the electrode by physical vapor deposition (PVD), followed by thermal annealing to construct primary gold seeds on the surface of the electrode. Then, gold seeds were grown by electrochemical deposition through gold salt. The cell-derived exosomes were successfully immobilized on the FTO electrode through the CD-151 antibody, and cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used in this research. In the CV method, the change in the current passing through the working electrode is measured so that the connection of exosomes causes the current to decrease. In the EIS method, surface resistance changes were investigated so that the binding of exosomes increased the surface resistance. Various concentrations of exosomes in both cell culture and blood serum samples were measured to test the sensitivity of the biosensor, which makes our biosensor capable of detecting 20 exosomes per milliliter. Full article

(This article belongs to the Special Issue Molecular Biology of Cancer—Implications for Diagnosis and Treatment 2.0)

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22 pages, 2662 KiB

Open AccessArticle

miRNAs in the Box: Potential Diagnostic Role for Extracellular Vesicle-Packaged miRNA-27a and miRNA-128 in Breast Cancer

by Cinzia Giordano, Felice Maria Accattatis, Luca Gelsomino, Piercarlo Del Console, Balázs Győrffy, Mario Giuliano, Bianca Maria Veneziani, Grazia Arpino, Carmine De Angelis, Pietro De Placido, Erica Pietroluongo, Francesco Zinno, Daniela Bonofiglio, Sebastiano Andò, Ines Barone and Stefania Catalano

Int. J. Mol. Sci. 2023, 24(21), 15695; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242115695 - 28 Oct 2023

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Abstract

Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer “theranostic” tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection. Full article

(This article belongs to the Special Issue Molecular Biology of Cancer—Implications for Diagnosis and Treatment 2.0)

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Review

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29 pages, 2328 KiB

Open AccessReview

Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements

by Edoardo Agosti, Marco Zeppieri, Lucio De Maria, Camilla Tedeschi, Marco Maria Fontanella, Pier Paolo Panciani and Tamara Ius

Int. J. Mol. Sci. 2023, 24(20), 15037; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242015037 - 10 Oct 2023

Cited by 6 | Viewed by 2902

Abstract

Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “glioblastomas,” “immunotherapies,” and “treatment.” The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability. Full article

(This article belongs to the Special Issue Molecular Biology of Cancer—Implications for Diagnosis and Treatment 2.0)

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15 pages, 999 KiB

Open AccessReview

Prostate Cancer Stem Cells: Biology and Treatment Implications

by Ioannis M. Koukourakis, Kalliopi Platoni, Vassilis Kouloulias, Stella Arelaki and Anna Zygogianni

Int. J. Mol. Sci. 2023, 24(19), 14890; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241914890 - 4 Oct 2023

Viewed by 1648

Abstract

Stem cells differentiate into mature organ/tissue-specific cells at a steady pace under normal conditions, but their growth can be accelerated during the process of tissue healing or in the context of certain diseases. It is postulated that the proliferation and growth of carcinomas are sustained by the presence of a vital cellular compartment resembling stem cells residing in normal tissues: ‘stem-like cancer cells’ or cancer stem cells (CSCs). Mutations in prostate stem cells can lead to the formation of prostate cancer. Prostate CSCs (PCSCs) have been identified and partially characterized. These express surface markers include CD44, CD133, integrin α2β1, and pluripotency factors like OCT4, NANOG, and SOX2. Several signaling pathways are also over-activated, including Notch, PTEN/Akt/PI3K, RAS-RAF-MEK-ERK and HH. Moreover, PCSCs appear to induce resistance to radiotherapy and chemotherapy, while their presence has been linked to aggressive cancer behavior and higher relapse rates. The development of treatment policies to target PCSCs in tumors is appealing as radiotherapy and chemotherapy, through cancer cell killing, trigger tumor repopulation via activated stem cells. Thus, blocking this reactive stem cell mobilization may facilitate a positive outcome through cytotoxic treatment. Full article

(This article belongs to the Special Issue Molecular Biology of Cancer—Implications for Diagnosis and Treatment 2.0)

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