Approach In Oncology Research Articles

Current and Future Developments in Radiation Oncology Approach for Rhabdomyosarcoma

Radiotherapy is an indispensable treatment modality in the management of rhabdomyosarcoma. Numerous efforts have been made to improve outcomes. The current thinking and future developments in the radiation oncology field about how to raise cure rates, especially in the highest-risk patients, are presented.

Molecular and immune landscape of melanoma: a risk stratification model for precision oncology

BackgroundMelanoma is a highly aggressive skin cancer with significant heterogeneity in immune infiltration and clinical outcomes. Accurate risk stratification is essential for improving personalized treatment strategies.MethodsThis study utilized data from The Cancer Genome Atlas (TCGA) to explore immune-related gene expression in melanoma. Single-sample gene set enrichment analysis (ssGSEA) was employed to classify patients into high and low immune groups. Tumor microenvironment (TME) characteristics, including immune cell infiltration, HLA gene expression, and TME scores, were analyzed. Prognostic genes were identified using univariate and multivariate Cox regression analyses. A risk score model and nomogram were constructed, and gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were conducted to explore relevant signaling pathways.ResultsssGSEA-based classification revealed significant differences between high and low immune groups in terms of immune infiltration and HLA gene expression. The risk model incorporated immune-related genes such as GBP2, SEMA4D, and KIR2DL4, which demonstrated distinct tumor expression profiles and strong prognostic value. GSEA and GSVA analyses uncovered critical immune-related and oncogenic pathways linked to risk stratification. A predictive nomogram integrating molecular risk scores and clinical variables improved prognostic accuracy. Computational immune deconvolution highlighted CD8+ T cell infiltration as a key prognostic factor. To validate the functional role of candidate genes, KIR2DL4 was silenced in A375 melanoma cells using shRNA. Knockdown efficiency was confirmed by qRT-PCR. Functional assays revealed that KIR2DL4 silencing significantly reduced cell proliferation, as assessed by MTT assay, and impaired migratory capacity, as demonstrated by wound healing assay. These in vitro findings support the computational predictions and suggest that KIR2DL4 may play a tumor-promoting role in melanoma.ConclusionThis study provides a robust immune-related prognostic model for melanoma. It underscores the value of immune gene expression and T cell infiltration, particularly CD8+ T cells, in predicting patient outcomes. The model facilitates personalized treatment decisions and advances precision oncology approaches in melanoma. The integration of transcriptomic analysis with experimental validation confirms the tumor-promoting role of KIR2DL4 and enhances the translational value of the model in guiding precision immunotherapy.

Advances in understanding therapeutic mechanisms of probiotics in cancer management, with special emphasis on breast cancer: A comprehensive review.

Advances in understanding therapeutic mechanisms of probiotics in cancer management, with special emphasis on breast cancer: A comprehensive review.

Drugging the Undruggable and beyond: Emerging precision oncology approaches to target acquired resistance to KRAS G12C and KRAS G12D inhibitors.

Drugging the Undruggable and beyond: Emerging precision oncology approaches to target acquired resistance to KRAS G12C and KRAS G12D inhibitors.

Targeting base excision repair in precision oncology.

Targeting base excision repair in precision oncology.

The Possibility of Plasma Membrane Transporters as Drug Targets in Oral Cancers.

Plasma membrane transporters are increasingly recognized as potential drug targets for oral cancer, particularly oral squamous cell carcinoma (OSCC). These transporters play crucial roles in cancer cell metabolism, drug resistance, and the tumor microenvironment, making them attractive targets for therapeutic intervention. Among the two main families of plasma membrane transporters, ATP-binding cassette (ABC) transporters have long been known to be involved in drug efflux and contribute to chemoresistance in cancer cells. On the other hand, solute carriers (SLCs) are also a family of transporters that facilitate the transport of various substrates, including nutrients and drugs, and have recently been shown to contribute to cancer chemosensitivity, metabolism, and proliferation. SLC transporters have been identified as potential cancer biomarkers and therapeutic targets, and their expression profiles suggest that they could be utilized in precision oncology approaches. We summarize previous reports on the expression and role of ABC and SLC transporters in oral cancer and discuss their potential as therapeutic targets.

Nonlinear Magnetic Response Measurements in Study of Magnetic Nanoparticles Uptake by Mesenchymal Stem Cells.

Stem cells therapies offer a promising approach in translational oncology, as well as in regenerative medicine due to the tropism of these cells to the damage site. To track the distribution of stem cells, the latter could be labeled by MRI-sensitive superparamagnetic (SPM) iron oxide nanoparticles. In the current study, magnetic properties of the magnetic nanoparticles (MNPs) incorporated into the bone marrow-derived fetal mesenchymal stem cells (FetMSCs) were evaluated employing nonlinear magnetic response measurements. Synthesized dextran-coated iron oxide nanoparticles were additionally characterized by X-ray diffraction, transmission electron microscopy, and dynamic light scattering. The MNP uptake by the FetMSCs 24 h following coincubation was studied by longitudinal nonlinear response to weak alternating magnetic field with registration of the second harmonic of magnetization. Subsequent data processing using a formalism based on the numerical solution of the Fokker-Planck kinetic equation allowed us to determine magnetic and dynamic parameters and the state of MNPs in the cells, as well as in the culture medium. It was found that MNPs formed aggregates in the culture medium; they were absorbed by the cells during coincubation. The aggregates exhibited SPM regime in the medium, and the parameters of the MNP aggregates remained virtually unchanged in the cells, indicating the preservation of the aggregation state of MNPs inside the cells. This implies also the preservation of the organic shell of the nanoparticles inside FetMSCs. The accumulation of MNPs by mesenchymal stem cells gradually increased with the concentration of MNPs. Thus, the study confirmed that the labeling of MSCs with MNPs is an effective method for subsequent cell tracking as incorporated nanoparticles retain their magnetic properties.

Laparoscopic surgery with rectal inversion and specimen extraction: A comparative analysis of efficacy in rectal cancer treatment

The objective of this study is to evaluate the efficacy of laparoscopic surgery combined with the rectal inversion and specimen extraction (RIES) technique for rectal cancer, focusing on both short-term and long-term outcomes. A retrospective comparative analysis was performed on 120 patients who underwent laparoscopic radical excision for rectal cancer from June 2017 to June 2021. Patients were categorized into two groups: Group RIES ([Formula: see text]), which received the novel RIES technique, and Group AIES ([Formula: see text]), which underwent the conventional abdominal incision for specimen extraction. Short-term outcomes, such as postoperative pelvic sepsis, temporary ileus, anastomotic leakage, and anastomotic stricture, were meticulously recorded. Long-term efficacy was evaluated through the 3-year overall survival (OS), disease-free survival (DFS), and local recurrence rate (LRR). The RIES group demonstrated a 3-year OS, DFS, and LRR of 86.2%, 77.6%, and 8.6%, respectively, with a low incidence of short-term complications. Comparatively, the AIES group showed a 3-year OS, DFS, and LRR of 83.9%, 74.2%, and 19.4%, respectively, with slightly higher rates of postoperative complications. Statistical analysis using the Student’s t-test, the chi-square ([Formula: see text]) test revealed no significant differences in the primary outcomes between the two groups, and suggested the noninferiority of the RIES technique. The study suggests that the RIES technique is a safe, feasible, and potentially functional and oncological superior approach to rectal cancer treatment, without compromising clinical efficacy. Further research is warranted to validate these findings in a larger, multicenter, and randomized controlled trial.

Volatile Organic Compounds in Biological Matrices as a Sensitive Weapon in Cancer Diagnosis

Diagnosis and intervention at the earliest stages of cancer are imperative for maximizing patient recovery outcomes and substantially increasing survival rates and quality of life. Recently, to facilitate cancer diagnosis, volatile organic compounds (VOCs) have shown potential with unique characteristics as cancer biomarkers. Various insects with sophisticated sensitivities of odor can be quickly and readily trained to recognize such VOCs using olfactory-linked skills. Furthermore, the approach to analyzing VOCs can be made using electronic noses, commonly referred to as e-noses. Using analytical instruments like GC-MS, LC-MS/MS, etc., chemical blends are separated into their constituent parts. The significance of odorant receptors in triggering neural responses to ambient compounds has received great attention in the last twenty years, particularly in the investigation of insect olfaction. Sensilla, a sophisticated olfactory neural framework, is regulated by a neuronal receptor composed of neuronal, non-neuronal, extracellular lymphatic fluid with an effectively generated shell. This review provides an in-depth exploration of the structural, functional, and signaling mechanisms underlying odorant sensitivities and chemical odor detection in the excretory products of cancer patients, addressing current challenges in VOC-based cancer diagnostics and innovative strategies for advancement while also envisioning the transformative role of artificial olfactory systems in the future of cancer detection. Furthermore, the article emphasizes recent preclinical and clinical advancements in VOC applications, highlighting their potential to redefine early diagnostic approaches in oncology.

Personalized Medical Approach in Gastrointestinal Surgical Oncology: Current Trends and Future Perspectives

Advances in artificial intelligence (AI), multi-omic profiling, and sophisticated imaging technologies have significantly advanced personalized medicine in gastrointestinal surgical oncology. These technological innovations enable precise patient stratification, tailored surgical strategies, and individualized therapeutic approaches, thereby significantly enhancing clinical outcomes. Despite remarkable progress, challenges persist, including the standardization and integration of diverse data types, ethical concerns regarding patient privacy, and rigorous clinical validation of predictive models. Addressing these challenges requires establishing international standards for data interoperability, such as Fast Healthcare Interoperability Resources, and adopting advanced security methods, such as homomorphic encryption, to facilitate secure multi-institutional data sharing. Moreover, ensuring model transparency and explainability through techniques such as explainable AI is critical for fostering trust among clinicians and patients. The successful integration of these advanced technologies necessitates strong multidisciplinary collaboration among surgeons, radiologists, geneticists, pathologists, and oncologists. Ultimately, the continued development and effective implementation of these personalized medical strategies complemented by human expertise promise a transformative shift toward patient-centered care, improving long-term outcomes for patients with gastrointestinal cancer.

Advancements in Metal Complexation of Pyridine Derivatives (2022-2024): A Pathway to Enhanced Anticancer Potency.

Cancer remains a major global health challenge, necessitating innovative therapies that selectively target cancer cells while sparing healthy tissues. Pyridine and its derivatives have gained prominence in medicinal chemistry for their structural diversity and biological activity. However, their therapeutic potential is often hindered by low bioavailability, poor solubility, and rapid metabolism. Metal complexation has emerged as a promising solution, with pyridine nitrogen serving as an excellent coordination site for transition metals. These pyridinemetal complexes enhance stability, bioavailability, and anticancer properties, exhibiting potent cytotoxicity through mechanisms like ROS generation, DNA intercalation, and apoptosis induction. This review highlights the latest progress (2022-2024) in the field, emphasizing the structural modifications, and mechanistic insights that have propelled pyridine-metal complexes as potent anticancer agents. Special attention is given to the role of metal complexation in enhancing the anticancer potency of pyridine derivatives, with examples of preclinical studies showing their efficacy against various cancer types. The findings emphasize the potential of pyridine-metal complexes as a transformative approach in oncology, bridging the gap between innovative chemical design and impactful therapeutic applications.

Abstract 7309: Investigating IL-1β signaling axis and inhibition strategies with small molecules in canine metastatic osteosarcoma: Insights for translational medicine

Abstract Introduction: Osteosarcoma (OS) is the most common bone tumor in pet dogs and people. While localized therapies, including surgery and ionizing radiation, effectively control bone-related events, options for slowing metastatic progression remain limited and only marginally active. Advances in drug delivery highlight the need for predictive animal tumor models to accelerate therapeutic development for humans. The clinical features, behavior, histopathology, treatment response, and genetics of OS in dogs closely mirror those in humans, making dogs an ideal comparative model. Dogs with spontaneous OS offer valuable insights into OS biology and are particularly useful for evaluating immunotherapeutic strategies. The pro-inflammatory effects of interleukin-1-beta (IL-1β) in the tumor microenvironment may hinder immunological responses against OS in both species. IL-1β is upregulated in the myeloid compartment of canine OS patients and facilitates metastatic progression in other cancers, including breast cancer. This study investigates the biological sources and role of IL-1β in OS metastatic biology and potential blocking strategies with small molecule inhibitors, offering insights for translational medicine. Methods: Canine OS cells, primary monocytes, monocyte-derived macrophages, and DH82 cells were used to investigate IL-1β secretion and receptor expression. Immunological and proliferative factors under IL-1β exposure were assessed by ELISA and clonogenic assays. RNA NanoString profiling was employed to characterize gene transcripts in both healthy canine lungs and metastatic OS lesions. A high-throughput screening approach evaluated the ability of 80, 000 small molecules to inhibit IL-1β intracellular downstream signaling and to inhibit IL-1β biological release and inflammasome activity. Results: Canine OS cells express receptors related to IL-1β signaling and secrete pro-metastatic factors upon IL-1β exposure. However, OS cells do not secrete IL-1β. Primary monocytes and DH82 cells secrete IL-1β in response to inflammasome and caspase activator molecules. Monocyte-derived M1 macrophages were found to release significantly higher amounts of IL-1β compared to M0 and M2 macrophages. Metastatic lesions in canine OS exhibited distinct gene transcript profiles. Small molecules and structure-related molecules with potent IL-1β inhibition activities were identified. Conclusions: Our study showed that IL-1β is secreted by monocytes and macrophages, not by OS cells. IL-1β induces the release of pro-metastatic factors by canine OS cells, suggesting its role in OS metastasis. Targeted inhibition of IL-1β may be a potential therapeutic strategy for controlling metastatic progression in OS and collectively underscore the potential value of comparative oncology approach towards successful translation medicine. Citation Format: Matheus Moreno Passos Barbosa, Vishnu V. Krishnamurthy, Timothy M. Fan. Investigating IL-1β signaling axis and inhibition strategies with small molecules in canine metastatic osteosarcoma: Insights for translational medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7309.

ATRX, OLIG2, MGMT, and IDH2 in Glioblastoma: Essential Molecular Mechanisms and Therapeutic Significance.

Background and Objectives: Glioblastoma (GBM) is among the most aggressive and lethal primary brain tumors, characterized by high heterogeneity, invasive growth, and resistance to conventional therapies. The 2021 WHO classification highlights the importance of molecular diagnostics, integrating genetic, transcriptomic, and epigenetic alterations alongside histological and immunohistochemical criteria. Materials and methods: Key molecular regulators, including ATRX, OLIG2, MGMT, and IDH2, play critical roles in chromatin remodeling, transcriptional reprogramming, DNA repair, and metabolic adaptation. However, their specific expression patterns and functional roles in GBM remain incompletely understood. This study utilizes publicly available data from The Cancer Genome Atlas (TCGA) to assess the transcriptional profiles of ATRX, OLIG2, MGMT, and IDH2 in GBM, aiming to identify potential biomarkers and therapeutic targets. Results: The expression analysis revealed that ATRX is downregulated at the gene level but overexpressed at the protein level, while OLIG2 is consistently overexpressed at both levels. MGMT showed no statistically significant changes in either gene or protein expression, whereas IDH2 was not significantly altered at the gene level but was downregulated at the protein level (p < 0.05). These discrepancies suggest potential post-transcriptional regulatory mechanisms influencing GBM molecular profiles. Notably, OLIG2 and MGMT expression correlated significantly with patient survival (p < 0.05), whereas ATRX and IDH2 did not reach statistical significance. Conclusions: Understanding these molecular relationships provides valuable insights into potential therapeutic strategies, paving the way for precision oncology approaches and combination therapies targeting multiple pathways simultaneously.

Unveiling the Role of JAK2/STAT3 signaling in chemoresistance of gynecological cancers: From mechanisms to therapeutic implications.

Unveiling the Role of JAK2/STAT3 signaling in chemoresistance of gynecological cancers: From mechanisms to therapeutic implications.

Investigating the Prognostic Role of Telomerase-Related Cellular Senescence Gene Signatures in Breast Cancer Using Machine Learning.

Background: Telomeres and cellular senescence are critical biological processes implicated in cancer development and progression, including breast cancer, through their influence on genomic stability and modulation of the tumor microenvironment. Methods: This study integrated bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) data to establish a gene signature associated with telomere maintenance and cellular senescence for prognostic prediction in breast cancer. Telomere-related genes (TEGs) and senescence-associated genes were curated from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A comprehensive machine learning framework incorporating 101 algorithmic combinations across 10 survival modeling approaches, including random survival forests and ridge regression, was employed to develop a robust prognostic model. Results: A set of 19 key telomere- and senescence-related genes was identified as the optimal prognostic signature. The model demonstrated strong predictive accuracy and was successfully validated in multiple independent cohorts. Functional enrichment analyses indicated significant associations with immune responses and aging-related pathways. Single-cell transcriptomic analysis revealed marked cellular heterogeneity, identifying distinct subpopulations (fibroblasts and immune cells) with divergent risk scores and biological pathway activity. Additionally, pseudo-time trajectory analysis and intercellular communication mapping provided insights into the dynamic evolution of the tumor microenvironment. Immunohistochemical (IHC) validation using data from the Human Protein Atlas confirmed differential protein expression between normal and tumor tissues for several of the selected genes, reinforcing their biological relevance and clinical utility. Conclusions: This study presents a novel 19-gene telomere- and senescence-associated signature with strong prognostic value in breast cancer. These findings enhance our understanding of tumor heterogeneity and may inform precision oncology approaches and future therapeutic strategies.

Health-Related Quality of Life in Breast Cancer Patients during Chemotherapy: A Cross-Sectional Study Using the EORTC QLQ-C30 and BR45.

To assess health-related quality of life (HRQoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Breast Cancer (EORTC QLQ-BR45) in conjunction with the Core questionnaire (EORTC QLQ-C30) in breast cancer patients receiving chemotherapy. This prospective, cross-sectional study was conducted in the oncology department of a tertiary care hospital for six months. Patients aged ≥18 years, diagnosed with breast cancer, and who had received at least three chemotherapy cycles were included in the study. The EORTC (QLQ-BR45 and QLQ-C30) questionnaires were used to assess HRQoL at chemotherapy cycle 3 (C3) and at C6 and C9. Data were analyzed using the Mann-Whitney U and Friedman tests for significance (p<0.05). The study showed improved global health status (C3:37.29%, C6:42.37%, C9:50%), high cognitive functioning (C3:89.83%, C6:91.53%, C9:96.55%), but decreasing emotional functioning (C3:66.10%, C6:49.15%, C9:36.21%). Symptom burden peaked in the sixth cycle but diminished over time with a trend towards fatigue (C3:64.41%, C6:67.80%, C9:37.93%), dyspnea (C3:54.24%, C6:55.93%, C9:32.76%), and pain (C3:42.37%, C6:52.54%, C9:34.48%). The study indicated satisfaction with body image (C3:61.02%, C6:67.80%, C9:67.24%) but decreased sexual functioning (C3:40.68%, C6:44.07%, C9:46.55%). Distress related to hair loss (p = 0.0001) increased over time. There was increased symptom burden at C6, underscoring the need for early interventions. We observed severe symptoms in elderly. However, lack of comorbidities and metastasis improved the emotional wellbeing in patients. These findings accentuate the importance of personalized and holistic care approaches in oncology.

Update on anaplastic thyroid cancer-What is relevant for surgeons?

Anaplastic thyroid cancer (ATC) is the rarest but also the most aggressive carcinoma entity of the thyroid gland. In recent years, treatment options have evolved and molecular oncological treatment approaches have gained in importance. The neoadjuvant use of these innovative therapies has the potential to convert previously unresectable tumors into aresectable state, thereby expanding surgical options and significantly improving the prognosis of patients. This article provides recommendations relevant for surgery for the diagnostics and treatment of ATC, based on acurrent literature review and the discussions of the S3guideline conferences.

Immune Modulation and Immunotherapy in Solid Tumors: Mechanisms of Resistance and Potential Therapeutic Strategies.

Understanding the modulation of specific immune cells within the tumor microenvironment (TME) offers new hope in cancer treatments, especially in cancer immunotherapies. In recent years, immune modulation and resistance to immunotherapy have become critical challenges in cancer treatments. However, novel strategies for immune modulation have emerged as promising approaches for oncology due to the vital roles of the immunomodulators in regulating tumor progression and metastasis and modulating immunological responses to standard of care in cancer treatments. With the progress in immuno-oncology, a growing number of novel immunomodulators and mechanisms are being uncovered, offering the potential for enhanced clinical immunotherapy in the near future. Thus, gaining a comprehensive understanding of the broader context is essential. Herein, we particularly summarize the paradoxical role of tumor-related immune cells, focusing on how targeted immune cells and their actions are modulated by immunotherapies to overcome immunotherapeutic resistance in tumor cells. We also highlight the molecular mechanisms employed by tumors to evade the long-term effects of immunotherapeutic agents, rendering them ineffective.

Bioelectromagnetism for Cancer Treatment-Modulated Electro-Hyperthermia.

Bioelectromagnetism has the potential to revolutionize cancer treatment by providing a noninvasive, targeted, and potentially more effective complement to traditional therapies. Among bioelectromagnetic techniques, modulated electro-hyperthermia (mEHT) stands out due to its unique characteristics, which have been supported by experimental evidence and clinical validation. Unlike conventional hyperthermia methods, mEHT leverages nonthermal bioelectromagnetic processes, offering a distinct and promising approach in oncology. This differentiation underscores the broader potential for bioelectromagnetic applications in cancer treatment, paving the way for innovative therapeutic strategies.

Abstract IA036: Using cancer stem cells to advance functional medicine in the era of precision oncology

Abstract Functional precision medicine (FPM) is a new approach in oncology that uses advanced technologies to personalize anticancer treatments based on the dynamic, functional characteristics of a patient's cancer at the molecular and cellular levels. Unlike traditional precision medicine, which often focuses on genomic information alone, FPM emphasizes the use of functional assays, such as cellular response profiling, to assess how a patient’s cancer reacts to various therapeutic agents in real time. This approach aims to bridge the gap between genetic susceptibilities and treatment outcomes, providing more accurate predictions of treatment efficacy and improving clinical decision-making. The utilization of functional diagnostic assays, such as the ChemoID assay, further enhances the potential of FPM. By directly assessing drug efficacy in patient-derived cancer stem cells (CSCs), the ChemoID assay provides crucial insights into tumor behavior and treatment resistance. The clinical validation of this assay in phase-3 randomized trials for glioblastoma and platinum-resistant ovarian cancer underscores its potential to significantly improve patient outcomes, particularly in cases where standard treatments have failed. The integration of functional assays like ChemoID into clinical trial designs represents a significant step forward in personalized cancer treatment. By bridging the gap between genomic information and treatment outcomes, this approach has the potential to transform the clinical management of cancer and improve the lives of patients. Clinical efficacy data from ChemoID randomized trials will be presented. Citation Format: Pier Paolo Claudio, Candace M Howard. Using cancer stem cells to advance functional medicine in the era of precision oncology [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA036.