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Biomedicines
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Advanced Cancer Diagnosis and Treatment: Third Edition
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Advanced Cancer Diagnosis and Treatment: Third Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 May 2026 | Viewed by 17666

Special Issue Editors

Dr. Takaaki Hirotsu

E-Mail Website
Guest Editor
Hirotsu Bio Science Inc., Chiyoda-Ku, Tokyo 102-0094, Japan
Interests: cancer biodiagnostics; early detection of cancers; cancer biomarkers; neurobiology of olfaction; nematode biology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Hideshi Ishii

E-Mail Website
Guest Editor
Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Suita, Japan
Interests: pancreatic cancer; gastrointestinal cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is the leading cause of death worldwide. The chances of survival increase with early cancer detection, but around half of all cancers are diagnosed at an advanced stage. Significant endeavors have been made to comprehend cancer's mechanisms, create accurate and sensitive diagnostic options, and produce efficient treatments. Over the past decade, advancements have been made in enhancing cancer screening programs and introducing innovative technologies to improve early cancer detection, with a particular focus on non-invasive methods. Novel approaches in cancer treatment are opening up new avenues for effective therapies.

Acknowledging the significant efforts made in combatting cancer, from academia to the private sector, in this Special Issue, we are seeking original research article or review submissions that present impactful advances in the development of cancer biology, diagnostics, and therapeutics in relation to one or more of, but not limited to, the following topics:

  • Cancer biology;
  • Molecular mechanisms of cancers;
  • Cancer epigenetics;
  • Resistance mechanism to conventional therapies;
  • Cancer biomarkers;
  • Early cancer detection;
  • Clinical investigations;
  • Cancer diagnostics;
  • Novel therapeutics;
  • Novel paradigms in cancer diagnosis and treatment.

Dr. Takaaki Hirotsu
Prof. Dr. Hideshi Ishii
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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines 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 2600 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

  • cancer biology
  • epigenetics
  • early detection
  • diagnosis
  • biodiagnosis
  • novel therapeutics
  • new paradigms

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Published Papers (6 papers)

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Research

Jump to: Review

25 pages, 2183 KB  
Article
Exploratory Analysis of Plasma Angiotensin-Converting Enzyme 2 and Angiotensin Peptides as Candidate Discriminatory Signals in Breast Cancer: A Pilot Case–Control Study
by Biwash Ghimire, Pradeep Giri, Susan Tavernier, Sarah E. Hobdey and Ali Aghazadeh-Habashi
Biomedicines 2026, 14(5), 1086; https://doi.org/10.3390/biomedicines14051086 - 12 May 2026
Viewed by 384
Abstract
Background: The renin-angiotensin system (RAS), traditionally known for its role in cardiovascular regulation, has also emerged as a key regulator of tumor progression and metastasis. Dysregulation of the RAS components has been implicated in breast cancer due to the significant presence of the [...] Read more.
Background: The renin-angiotensin system (RAS), traditionally known for its role in cardiovascular regulation, has also emerged as a key regulator of tumor progression and metastasis. Dysregulation of the RAS components has been implicated in breast cancer due to the significant presence of the RAS-related proteins in the breast tissue. This study aims to identify the dysregulated RAS components and investigate their potential as candidate biomarkers. Methods: A pilot case–control study was carried out with 21 treatment-naïve breast cancer patients and 17 healthy controls. Plasma levels of Ang 1-7, Ang II, ACE2 and selected cytokines (IL-6, IL-8, IL-10 and IFN-γ) were measured using LC-MS/MS and ELISA. ROC curves were used to assess changes in biomarker levels across the RAS components. Results: This pilot cohort showed evidence of altered circulating RAS-related analytes and IL-10 in treatment-naïve breast cancer patients compared with controls. The ratio of Ang 1-7/Ang II was reduced by over two-fold in breast cancer patients (p = 0.0442). While plasma ACE2 was significantly elevated in breast cancer patients (p = 0.0005), IL-10 was significantly suppressed (p = 0.0420). In exploratory logistic regression analysis, ACE2 showed potential as a classifier with improved discrimination when combined with Ang 1-7 and Ang II (AUC = 0.9396 [95% bootstrap CI: 0.84–1.00], accuracy = 92.59% at the Youden-optimized threshold). However, due to the small sample size and methodological limitations, these findings require further validation. Conclusions: In this exploratory pilot study, plasma ACE2, the Ang 1-7/Ang II ratio, and IL-10 showed promising discriminatory performance. However, these findings are hypothesis-generating and require external validation in larger, prospectively enrolled cohorts before any clinical inference can be drawn. Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)
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13 pages, 1488 KB  
Article
Deciphering the Causative Role of a Novel APC Gene Variant in Attenuated Familial Adenomatous Polyposis Using Germline DNA-RNA Paired Testing
by Giovanna Forte, Candida Fasano, Matteo Iacoviello, Valentina Grossi, Martina Lepore Signorile, Katia De Marco, Paola Sanese, Antonia Lucia Buonadonna, Andrea Manghisi, Nicoletta Maria Tutino, Vittoria Disciglio and Cristiano Simone
Biomedicines 2026, 14(1), 87; https://doi.org/10.3390/biomedicines14010087 - 1 Jan 2026
Viewed by 1101
Abstract
Background/Objectives: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by pathogenic variants in the adenomatous polyposis coli (APC) gene. Its attenuated form (AFAP) is characterized by fewer colorectal polyps and later onset of colorectal cancer. We aimed to [...] Read more.
Background/Objectives: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by pathogenic variants in the adenomatous polyposis coli (APC) gene. Its attenuated form (AFAP) is characterized by fewer colorectal polyps and later onset of colorectal cancer. We aimed to characterize the molecular effects of a novel APC gene variant (NM_000038.6: c.1620_1624delinsT) identified in a patient with AFAP. Methods: A 56-year-old man with the AFAP phenotype underwent germline testing via a multigene NGS panel, which identified a novel APC gene variant (NM_000038.6: c.1620_1624delinsT). In silico analyses predicted disruption of the canonical donor splice site and a frameshift followed by the introduction of a premature stop codon. The transcriptional impact of the identified APC gene variant was investigated by mRNA analysis. Results: mRNA analysis revealed two distinct APC transcripts: the first transcript led to a truncated protein (p.Leu540PhefsTer8), and the second transcript lacked exon 12, resulting in an in-frame 26 amino acid deletion of APC protein (p.Ala517_Gly542del). The transcript lacking exon 12 was more abundant than the transcript with a premature stop codon, likely due to degradation through nonsense-mediated decay. Conclusions: The APC gene variant (NM_000038.6: c.1620_1624delinsT) exhibits a dual transcriptional effect, revealing its pathogenic role in AFAP. This study highlights the diagnostic value of combined DNA–RNA germline testing for improving the clinical classification of novel APC gene variants and their genotype–phenotype correlations in FAP. Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)
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Review

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25 pages, 1428 KB  
Review
Beyond Binary: A Machine Learning Framework for Interpreting Organismal Behavior in Cancer Diagnostics
by Aya Hasan Alshammari, Monther F. Mahdi, Takaaki Hirotsu, Masayo Morishita, Hideyuki Hatakeyama and Eric di Luccio
Biomedicines 2025, 13(10), 2409; https://doi.org/10.3390/biomedicines13102409 - 30 Sep 2025
Viewed by 2264
Abstract
Organismal biosensing leverages the olfactory acuity of living systems to detect volatile organic compounds (VOCs) associated with cancer, offering a low-cost and non-invasive complement to conventional diagnostics. Early studies demonstrate its feasibility across diverse platforms. In C. elegans, chemotaxis assays on urine [...] Read more.
Organismal biosensing leverages the olfactory acuity of living systems to detect volatile organic compounds (VOCs) associated with cancer, offering a low-cost and non-invasive complement to conventional diagnostics. Early studies demonstrate its feasibility across diverse platforms. In C. elegans, chemotaxis assays on urine samples achieved sensitivities of 87–96% and specificities of 90–95% in case–control cohorts (n up to 242), while calcium imaging of AWC neurons distinguished breast cancer urine with ~97% accuracy in a small pilot cohort (n ≈ 40). Trained canines have identified prostate cancer from urine with sensitivities of ~71% and specificities of 70–76% (n ≈ 50), and AI-augmented canine breath platforms have reported accuracies of ~94–95% across ~1400 participants. Insects such as locusts and honeybees enable ultrafast neural decoding of VOCs, achieving 82–100% classification accuracy within 250 ms in pilot studies (n ≈ 20–30). Collectively, these platforms validate the principle that organismal behavior and neural activity encode cancer-related VOC signatures. However, limitations remain, including small cohorts, methodological heterogeneity, and reliance on binary outputs. This review proposes a Dual-Pathway Framework, where Pathway 1 leverages validated indices (e.g., the Chemotaxis Index) for high-throughput screening, and Pathway 2 applies machine learning to high-dimensional behavioral vectors for cancer subtyping, staging, and monitoring. By integrating these approaches, organismal biosensing could evolve from proof-of-concept assays into clinically scalable precision diagnostics. Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)
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16 pages, 297 KB  
Review
Adrenal Incidentaloma: From Silent Diagnosis to Clinical Challenge
by Alexandra Mirica, Dana-Mihaela Tilici, Diana Loreta Paun, Ana Maria Arnautu, Victor Nimigean and Sorin Paun
Biomedicines 2025, 13(9), 2298; https://doi.org/10.3390/biomedicines13092298 - 19 Sep 2025
Cited by 4 | Viewed by 2509
Abstract
The widespread use of advanced imaging techniques has led to a rising incidence of adrenal incidentalomas (AIs), asymptomatic adrenal masses discovered during imaging for non-adrenal-related conditions. AIs represent a diagnostic and therapeutic challenge due to their varied etiology, secretory potential, and potential for [...] Read more.
The widespread use of advanced imaging techniques has led to a rising incidence of adrenal incidentalomas (AIs), asymptomatic adrenal masses discovered during imaging for non-adrenal-related conditions. AIs represent a diagnostic and therapeutic challenge due to their varied etiology, secretory potential, and potential for malignancy. This review aims to provide a comprehensive overview of the current knowledge on adrenal incidentalomas, focusing on their pathogenesis, diagnostic work-up, imaging features, hormonal evaluation, and evidence-based management, with a special emphasis on autonomous cortisol secretion (ACS). A thorough narrative review of the literature from the past two decades was conducted, synthesizing data from key international guidelines (ESE/ENSAT), observational studies, meta-analyses, and case series regarding the evaluation and treatment of AI. AI represents an increasingly relevant clinical condition requiring a multidisciplinary, personalized approach. Prompt endocrine and radiological evaluation is essential to identify hormonally active or potentially malignant tumors. The complexity of the natural history of AI and the evolving understanding of ACS underline the need for tailored follow-up and management strategies. Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)
31 pages, 3657 KB  
Review
Lipid Metabolism Reprogramming in Cancer: Insights into Tumor Cells and Immune Cells Within the Tumor Microenvironment
by Rundong Liu, Chendong Wang, Zhen Tao and Guangyuan Hu
Biomedicines 2025, 13(8), 1895; https://doi.org/10.3390/biomedicines13081895 - 4 Aug 2025
Cited by 11 | Viewed by 7303
Abstract
This review delves into the characteristics of lipid metabolism reprogramming in cancer cells and immune cells within the tumor microenvironment (TME), discussing its role in tumorigenesis and development and analyzing the value of lipid metabolism-related molecules in tumor diagnosis and prognosis. Cancer cells [...] Read more.
This review delves into the characteristics of lipid metabolism reprogramming in cancer cells and immune cells within the tumor microenvironment (TME), discussing its role in tumorigenesis and development and analyzing the value of lipid metabolism-related molecules in tumor diagnosis and prognosis. Cancer cells support their rapid growth through aerobic glycolysis and lipid metabolism reprogramming. Lipid metabolism plays distinct roles in cancer and immune cells, including energy supply, cell proliferation, angiogenesis, immune suppression, and tumor metastasis. This review focused on shared lipid metabolic enzymes and transporters, lipid metabolism-related oncogenes and non-coding RNAs (ncRNAs) involved in cancer cells, and the influence of lipid metabolism on T cells, dendritic cells (DCs), B cells, tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), and natural killer cells (NKs) within TME. Additionally, the role of lipid metabolism in tumor diagnosis and prognosis was explored, and lipid metabolism-based anti-tumor treatment strategies were summarized, aiming to provide new perspectives for achieving precision medicine. Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)
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21 pages, 1962 KB  
Review
From Survival to Parenthood: The Fertility Journey After Childhood Cancer
by Sofia Rahman, Veronica Sesenna, Diana Osorio Arce, Erika Maugeri and Susanna Esposito
Biomedicines 2025, 13(8), 1859; https://doi.org/10.3390/biomedicines13081859 - 30 Jul 2025
Cited by 1 | Viewed by 3413
Abstract
Background: The advances in cancer diagnosis and treatment have significantly improved survival rates in pediatric patients, with five-year survival now exceeding 80% in many high-income countries. However, these life-saving therapies often carry long-term consequences, including impaired fertility. The reproductive health of childhood [...] Read more.
Background: The advances in cancer diagnosis and treatment have significantly improved survival rates in pediatric patients, with five-year survival now exceeding 80% in many high-income countries. However, these life-saving therapies often carry long-term consequences, including impaired fertility. The reproductive health of childhood cancer survivors has emerged as a key issue in survivorship care. Objective: This narrative review aims to examine the gonadotoxic effects of cancer treatments on pediatric patients, evaluate fertility preservation strategies in both males and females, and provide guidance on the long-term monitoring of reproductive function post treatment. Methods: A comprehensive literature review was conducted using PubMed, including randomized trials, cohort studies, and clinical guidelines published up to March 2024. The keywords focused on pediatric oncology, fertility, and reproductive endocrinology. Studies were selected based on relevance to treatment-related gonadotoxicity, fertility preservation options, and follow-up care. Results: Radiotherapy and alkylating agents pose the highest risk to fertility. Postpubertal patients have access to standardized preservation techniques, while prepubertal options remain experimental. Long-term effects include premature ovarian insufficiency, azoospermia, hypogonadism, and uterine dysfunction. The psychosocial impacts, especially in female survivors, are profound and often overlooked. Conclusions: Fertility preservation should be discussed at diagnosis and integrated into treatment planning in pediatric patients with cancer. While options for postpubertal patients are established, more research is needed to validate safe and effective strategies for younger populations. A multidisciplinary approach and long-term surveillance are essential for safeguarding future reproductive potential in childhood cancer survivors. Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)
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