Field Of Oncology Research Articles

Microbiota in tumors: new factor influencing cancer development.

Tumor microbiota research is a new field in oncology. With the advancement of high-throughput sequencing, there is growing evidence that a microbial community exists within tumor tissue. How these bacteria access tumor cells varies, including through the invasion of mucous membranes, the bloodstream, or the gut-organ axis. Previous literature has shown that microbes promote the development and progression of cancer through various mechanisms, such as affecting the host's immune system, promoting inflammation, regulating metabolism, and activating invasion and transfer. The study of the tumor microbiota offers a new perspective for the diagnosis and treatment of cancer, and it holds the potential for the development of new diagnostic tools and therapies. The role of the tumor microbiota in the pathogenesis of cancer is becoming increasingly evident, and future research will continue to uncover the specific mechanisms of action of these microbes, potentially shedding light on new strategies and methods for cancer prevention and therapy. This article reviews the latest advancements in this field, including how intratumor microbes migrate, their carcinogenic mechanisms, and the characteristics of different types of tumor microbes as well as the application of relevant methods in tumor microbiota research and the clinical values of targeting tumor microbes in cancer therapy.

Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.

Studies of carcinogenic metabolism have shown that cancer cells have significant metabolic adaptability and that their metabolic dynamics undergo extensive reprogramming, which is a fundamental feature of cancer. The Warburg effect describes the preference of cancer cells for glycolysis over oxidative phosphorylation (OXPHOS), even under aerobic conditions. However, metabolic reprogramming in cancer cells involves not only glycolysis but also changes in lipid and amino acid metabolism. The mechanisms of these metabolic shifts are critical for the discovery of novel cancer therapeutic targets. Despite advances in the field of oncology, chemotherapy resistance, including multidrug resistance, remains a challenge. Research has revealed a correlation between metabolic reprogramming and anticancer drug resistance, but the underlying complex mechanisms are not fully understood. In addition, small extracellular vesicles (sEVs) may play a role in expanding metabolic reprogramming and promoting the development of drug resistance by mediating intercellular communication. The aim of this review is to assess the metabolic reprogramming processes that intersect with resistance to anticancer therapy, with particular attention given to the changes in glycolysis, lipid metabolism, and amino acid metabolism that accompany this phenomenon. In addition, the role of sEVs in disseminating metabolic reprogramming and promoting the development of drug-resistant phenotypes will be critically evaluated.

Assessing Breast Cancer through Tumor Microenvironment Mapping of Collagen and Other Biomolecule Spectral Fingerprints─A Review.

Breast cancer is a major challenge in the field of oncology, with around 2.3 million cases and around 670,000 deaths globally based on the GLOBOCAN 2022 data. Despite having advanced technologies, breast cancer remains the major type of cancer among women. This review highlights various collagen signatures and the role of different collagen types in breast tumor development, progression, and metastasis, along with the use of photoacoustic spectroscopy to offer insights into future cancer diagnostic applications without the need for surgery or other invasive techniques. Through mapping of the tumor microenvironment and spotlighting key components and their absorption wavelengths, we emphasize the need for extensive preclinical and clinical investigations.

The Comparative Oncology of Canine Malignant Melanoma in Targeted Therapy: A Systematic Review of In Vitro Experiments and Animal Model Reports

Canine malignant melanoma (CMM) is highly aggressive and mostly located in the oral cavity. CMM is the predominant type of canine oral malignancy and shows striking homologies with human mucosal melanoma. In comparative oncology, canine oral melanomas (COMs), as spontaneous tumor models, have the potential to acquire a unique value as a translational model of rare human melanoma subtypes. This review aims to provide a comprehensive summary of targeted therapies for canine malignant melanoma and to enrich the field of comparative oncology. Following the PRISMA guidelines, a comprehensive literature search was conducted across databases for studies from 1976 to April 2024. Studies were selected based on their relevance to targeted treatments. A total of 30 studies met the inclusion criteria. Based on the treatment approaches, the studies were further categorized into immunotherapies, small molecule signaling inhibitors, indirect kinase inhibitors, and other alternative strategies. Some treatments have been shown to result in stable disease or partial response, accounting for 29% (monoclonal antibody) and 76.5% (micro-RNA therapies) in clinical trials. Moreover, in vitro experiments of small molecule inhibitors, including cell signaling inhibitors and indirect kinase inhibitors, have shown the potential to be an effective treatment option for the development of therapeutic strategies in canine malignant melanoma. The observed response in in vitro experiments of CMM (particularly the oral and certain cutaneous subtypes) to drugs used in the treatment of human melanoma underlines the resemblance to human melanoma, therefore supporting the notion that CMM may be a valuable model for understanding rare human melanoma subtypes and exploring potential therapeutic avenues in preclinical trials. Finally, this literature review serves as a valuable resource for the development of therapeutic strategies for CMM and highlights the potential for translating these findings to human cancer treatment.

A heterotypic tumor-on-a-chip platform for user-friendly combinatorial chemotherapeutic testing

BackgroundThree-dimensional (3D) tumor microdevices are promising platform for biomimetic antitumor prediction and high-throughput chemotherapeutic screening and play crucial roles in the exploration of cancer-associated pharmaceutics and therapeutics. Traditional cell manipulation tools (e.g., non-adhesive surfaces and hanging drops) and recent microengineered systems (e.g., microfluidic chips and micropatterned array chips) have progressed in terms of microscale control, substantial tumor production, programmable drug combinations, and throughput analysis. However, establishing a facile 3D tumor microdevice to construct heterotypic tumor-microenvironmental profiles and for throughput, implementable, multi-instrument-compatible analysis of chemotherapies to advance consumer-grade tumor modelling tools is still being explored. ResultsIn this study, we present a facilely operated tumor-on-a-chip platform for massive production of heterotypic 3D tumors and diverse investigations of combinatorial chemotherapy screening. Large quantity of heterotypic tumor generation with high geometric controllability (size difference: 19.6 μm) and operational repeatability (n = 10) was achieved using simple-to-fabricate micropatterned chips. Multiple characteristics of solid tumors, including phenotypic gradients (viability and proliferation) and heterogeneous cellular compositions (multi-cell participation and stroma composition), were reproduced in heterotypic tumors, being more biomimetic than homotypic tumors. We completed the user-friendly analytical evaluation of individual and combinatorial drug therapies, and demonstrated the high applicability of the platform in biomimetic tumor-related large-scale manipulation and on-chip analysis, as well as its high compatibility for off-chip detection. The entire operative process during tumor production and chemotherapy only requires the routine and easy-to-master pipetting manipulation. SignificanceThe establishment of a biomimetic and easy-to-use 3D tumor platform and the large-scale screening-like evaluation of combinatorial chemotherapies based on the usage of the micropatterned chip was achieved in a user-friendly manner. This advancement has significant application potential in the fields of oncology, drug discovery, and tissue engineering, and is expected to be valuable for developing accessible and generalizable tumor-on-a-chip microsystems for exploring cancer therapies.

Dr. V. Shanta: A Beacon of Hope for Indian Oncology.

Dr. V. Shanta was a pioneer in the field of oncology in India. Born into a family known for scientific contributions, she was inspired to pursue medicine and eventually joined the Cancer Institute in Chennai in 1955. Her efforts transformed the institute into a world-renowned center for cancer treatment, research, and education. Dr. Shanta's work focused on making cancer care accessible and affordable, particularly for the underprivileged, and made possible the establishment of regional cancer centers to reach rural and remote populations. She was also instrumental in introducing modern cancer therapies in India, including chemotherapy and radiation therapy, and tailored treatment protocols for Indian patients. Her work in cancer research was phenomenal and influenced national cancer policies. As a leader, she served on several expert committees, including those of the World Health Organization, and was honored with India's highest civilian awards for her contributions to medicine. Beyond her professional achievements, Dr. Shanta was a compassionate healer who believed in holistic care. She addressed the physical, emotional, and psychological needs of her patients and left a lasting impact on patients. Dr. V. Shanta's life and work continue to inspire generations and her legacy remains a beacon of hope in the fight against cancer.

SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment.

Despite significant advancements in the field of oncology, cancers still pose one of the greatest challenges of modern healthcare. Given the cytoskeleton's pivotal role in regulating mechanisms critical to cancer development, further studies of the cytoskeletal elements could yield new practical applications. Septins represent a group of relatively well-conserved GTP-binding proteins that constitute the fourth component of the cytoskeleton. Septin 9 (SEPT9) has been linked to a diverse spectrum of malignancies and appears to be the most notable septin member in that category. SEPT9 constitutes a biomarker of colorectal cancer (CRC) and has been positively correlated with a high clinical stage in breast cancer, cervical cancer, and head and neck squamous cell carcinoma. SEPT9_i1 represents the most extensively studied isoform of SEPT9, which substantially contributes to carcinogenesis, metastasis, and treatment resistance. Nevertheless, the mechanistic basis of SEPT9_i1 oncogenicity remains to be fully elucidated. In this review, we highlight SEPT9's and SEPT9_i1's structures and interactions with Hypoxia Inducible Factor α (HIF-1 α) and C-Jun N-Terminal Kinase (JNK), as well as discuss SEPT9_i1's contribution to aneuploidy, cell invasiveness, and taxane resistance-key phenomena in the progression of malignancies. Finally, we emphasize forchlorfenuron and other septin inhibitors as potential chemotherapeutics and migrastatics.

Therapy-related myelodysplastic syndromes and acute myeloid leukemia

Progress always comes at a price: the field of oncology has seen unprecedented progress in treatment options recently for many solid and hematologic cancers. Unfortunately, these long-term survivors of prior cancer and cytotoxic therapy exposure are at higher risk of therapy-related myelodysplastic syndromes/acute myeloid leukemia (t-MDS/AML.) T-MDS/AML is a myeloid malignancy which occur after exposure to chemotherapy or radiation therapy for unrelated malignancy. T-MDS/AML is associated with adverse cytogenomic features and poor prognosis. While advances in the field of clonal hematopoiesis and germline variants has unraveled the molecular underpinnings of t-MDS/AML, we have miles to go in terms of t-MDS/AML directed therapy and improvement in outcomes. In this review, we discuss the epidemiology of t-MDS/AML, clinical and biological insights, evolution of t-MDS/AML and available treatment options.

Assessing The Thermal Damage Induced By Radiofrequency Ablation for Localized Liver Cancer

Abstract Clinical trials are already established for high-temperature treatment of localized cancer, i.e., rise of tissue temperature to more than 550 C as an effective non-invasive method for the treatment of localized cancer. However, as the computational techniques and capacity have enhanced considerably personalized treatment planning has become a manured tool. In the present investigation, a novel treatment planning framework is being proposed for radiofrequency ablation of cancer tissue based on the tomographic image-based actual model. In patient-specific modelling, different thermal parameters like temperature history during ablation, and thermal damage profile have been virtually determined based on Penne's bioheat transfer model with appropriate boundary conditions. This advancement promises to significantly enhance the capabilities of healthcare practitioners in tailoring personalized treatment strategies for their clinical cases. By leveraging simulation outcomes, clinicians can precisely determine the most effective parameters, such as ablation power and frequency. Unfortunately, the current landscape in India presents a scarcity of specialized medical experts in the field of ablation oncology. Moreover, those who practice in this niche often rely on empirical charts rather than data-driven approaches, highlighting a critical need for increased expertise and the integration of advanced simulation technology to optimize cancer tissue ablation procedures. Last but not least optimizing different operating parameters of RF in this patient-centric approach for accurate treatment has also been discussed.

William Coley: The Pioneer and the Father of Immunotherapy.

William Coley was an unacclaimed hero of early cancer treatment. His work is often overshadowed by more recent advancements in immunotherapy. Coley's innovative work in the 1910s and 1930s laid the groundwork for what would become a major field in oncology. His experiments with bacterial vaccines by making use of the immune system to combat cancer preceded contemporary immunotherapy for several decades. This review provides a comprehensive exploration of Coley's life, his groundbreaking research, the socio-scientific challenges he faced, and his lasting impact on cancer treatment. Even though he faced lots of initial resistance and challenges, Coley's work has influenced modern immunotherapy practices.

Cancer Patient-Derived Cell-Based Models: Applications and Challenges in Functional Precision Medicine.

The field of oncology has witnessed remarkable progress in personalized cancer therapy. Functional precision medicine has emerged as a promising avenue for achieving superior treatment outcomes by integrating omics profiling and sensitivity testing of patient-derived cancer cells. This review paper provides an in-depth analysis of the evolution of cancer-directed drugs, resistance mechanisms, and the role of functional precision medicine platforms in revolutionizing individualized treatment strategies. Using two-dimensional (2D) and three-dimensional (3D) cell cultures, patient-derived xenograft (PDX) models, and advanced functional assays has significantly improved our understanding of tumor behavior and drug response. This progress will lead to identifying more effective treatments for more patients. Considering the limited eligibility of patients based on a genome-targeted approach for receiving targeted therapy, functional precision medicine provides unprecedented opportunities for customizing medical interventions according to individual patient traits and individual drug responses. This review delineates the current landscape, explores limitations, and presents future perspectives to inspire ongoing advancements in functional precision medicine for personalized cancer therapy.

The Oncoprotein Fra-2 Drives the Activation of Human Endogenous Retrovirus Env Expression in Adult T-Cell Leukemia/Lymphoma (ATLL) Patients.

Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs' aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8+-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.

Multidisciplinary Team Meetings: Barriers to Implementation in Cancer Care.

The multidisciplinary team meeting has become a fundamental component of cancer care across most of Europe, North America, and Australia. In certain institutions, it holds a mandatory role in the treatment planning of all patients with cancer. Although the multidisciplinary team meeting has demonstrated improved adherence to clinical protocols in the oncology field and serves as a valuable educational tool for clinicians, it is difficult to truly gauge its impact on clinical outcomes due to the wide heterogeneity in interinstitutional meeting practices and the varied data reporting clinical outcomes. This literature review will provide an overview of the history and contextual role of the multidisciplinary team meeting in cancer management and discuss the barriers to its implementation, offering means to navigate these barriers. This review will also explore the barriers to adherence to treatment recommendations offered by the multidisciplinary team meeting in cancer care, through the lens of the patient and health care provider.

Specific imaging of CD8 + T-Cell dynamics with a nanobody radiotracer against human CD8β.

While immunotherapy has revolutionized the oncology field, variations in therapy responsiveness limit the broad applicability of these therapies. Diagnostic imaging of immune cell, and specifically CD8+ T cell, dynamics could allow early patient stratification and result in improved therapy efficacy and safety. In this study, we report the development of a nanobody-based immunotracer for non-invasive SPECT and PET imaging of human CD8+ T-cell dynamics. Nanobodies targeting human CD8β were generated by llama immunizations and subsequent biopanning. The lead anti-human CD8β nanobody was characterized on binding, specificity, stability and toxicity. The lead nanobody was labeled with technetium-99m, gallium-68 and copper-64 for non-invasive imaging of human T-cell lymphomas and CD8+ T cells in human CD8 transgenic mice and non-human primates by SPECT/CT or PET/CT. Repeated imaging of CD8+ T cells in MC38 tumor-bearing mice allowed visualization of CD8+ T-cell dynamics. The nanobody-based immunotracer showed high affinity and specific binding to human CD8 without unwanted immune activation. CD8+ T cells were non-invasively visualized by SPECT and PET imaging in naïve and tumor-bearing mice and in naïve non-human primates with high sensitivity. The nanobody-based immunotracer showed enhanced specificity for CD8+ T cells and/or faster in vivo pharmacokinetics compared to previous human CD8-targeting immunotracers, allowing us to follow human CD8+ T-cell dynamics already at early timepoints. This study describes the development of a more specific human CD8+ T-cell-targeting immunotracer, allowing follow-up of immunotherapy responses by non-invasive imaging of human CD8+ T-cell dynamics.

More than meets the eye: Augmented reality in surgical oncology.

In the field of surgical oncology, there has been a desire for innovative techniques to improve tumor visualization, resection, and patient outcomes. Augmented reality (AR) technology superimposes digital content onto the real-world environment, enhancing the user's experience by blending digital and physical elements. A thorough examination of AR technology in surgical oncology has yet to be performed. A scoping review of intraoperative AR in surgical oncology was conducted according to the guidelines and recommendations of The Preferred Reporting Items for Systematic Review and Meta-analyzes Extension for Scoping Reviews (PRISMA-ScR) framework. All original articles examining the use of intraoperative AR during surgical management of cancer were included. Exclusion criteria included virtual reality applications only, preoperative use only, fluorescence, AR not specific to surgical oncology, and study design (reviews, commentaries, abstracts). A total of 2735 articles were identified of which 83 were included. Most studies (52) were performed on animals or phantom models, while the remaining included patients. A total of 1112 intraoperative AR surgical cases were performed across the studies. The most common anatomic site was brain (20 articles), followed by liver (16), renal (9), and head and neck (8). AR was most often used for intraoperative navigation or anatomic visualization of tumors or critical structures but was also used to identify osteotomy or craniotomy planes. AR technology has been applied across the field of surgical oncology to aid in localization and resection of tumors.

Shaping the future of cancer treatment: The commitment of medical physicists

The incorporation of medical physics into the field of oncology has profoundly changed the ways in which cancer is diagnosed and treated. This article highlights the essential roles that medical physicists play in cancer care, demonstrating how principles from physics improve various aspects of oncology practices. Our analysis reveals that medical physics plays a fundamental role in optimizing various oncological procedures, thereby revolutionizing the management of cancer. Specifically, medical physicists are integral to critical areas such as radiation therapy planning, surgical navigation, and quality assurance, which collectively facilitate personalized and effective treatment strategies for patients. By working closely with healthcare professionals, medical physicists help ensure patients receive top-notch care while minimizing side effects associated with treatments. Their dedication to innovation and research is essential for improving both patient outcomes and quality of life throughout the cancer journey. The ongoing partnership between medical physicists and clinicians is instrumental in propelling advancements in oncology research and clinical practices, leveraging physics principles alongside state-of-the-art technologies to enhance cancer management. As medical physicists commit to excellence and patient-centered practices, they are at the forefront of transforming oncology care, promising improved hope and outcomes for those battling cancer. This collaborative effort ensures a bright future for cancer treatment, where the integration of physics not only optimizes therapeutic approaches but also fosters a comprehensive understanding of cancer care.

FTO in Lung Cancer: Its Progression and Therapeutic Potential.

One of the most fatal and frequent malignancies on the planet is lung cancer. Its occurrence and development are the results of multifactorial and multigenic interactions. In recent years, RNA N6-methyladenosine transferase (FTO) has gained significant attention in the field of oncology. FTO is the first RNA demethylase to be found to control target mRNA demethylation. The growth, proliferation, and metastasis of tumor cells are greatly influenced by FTO. Recent studies have found that imbalanced m6A methylation regulatory proteins can induce disruption of downstream RNA metabolism, strongly affecting tumor development. This paper provides an overview of the relationship between FTO and lung cancer, discussing the mechanisms by which FTO is involved in lung cancer and its potential clinical applications.

Contemporary Molecular Markers for Predicting Systemic Treatment Response in Urothelial Bladder Cancer: A Narrative Review.

The search for dependable molecular biomarkers to enhance routine clinical practice is a compelling challenge across all oncology fields. Urothelial bladder carcinoma, known for its significant heterogeneity, presents difficulties in predicting responses to systemic therapies and outcomes post-radical cystectomy. Recent advancements in molecular cancer biology offer promising avenues to understand the disease's biology and identify emerging predictive biomarkers. Stratifying patients based on their recurrence risk post-curative treatment or predicting the efficacy of conventional and targeted therapies could catalyze personalized treatment selection and disease surveillance. Despite progress, reliable molecular biomarkers to forecast responses to systemic agents, in neoadjuvant, adjuvant, or palliative treatment settings, are still lacking, underscoring an urgent unmet need. This review aims to delve into the utilization of current and emerging molecular signatures across various stages of urothelial bladder carcinoma to predict responses to systemic therapy.

The Fletcher-Cox Pathway: A Unique View on Clinical Trial Education

PurposeThere currently are no established formal mentorship and training program for radiation oncology (RO) trainees to learn trial design, creation, writing, or implementation. There only exists informal training on analyzing clinical trials in RO residency programs. The integration of a longitudinal formal training and mentorship program for clinical trialists - consisting of clinical trial education, design, mentorship, and implementation during the RO residency education will give residents not only formal teaching in the subject, but strong tools and requisite mentorship in hopes to help them succeed as future academic physicians and leaders in the field of radiation oncology. Methods and MaterialsWe developed a clinical trial training pathway in 2018 at XXX, proposing it as a pilot program. The “Fletcher-Cox Pathway” was accepted with a highly positive response by trainees. and is is now offered as a standard option to RO trainees at our institution. ResultsWith the guidance of their principal investigator (PI), residents participating in this pathway design and submit a clinical trial for institutional review board (IRB) review. In 2019, after implementation of the pilot program, 4 of the incoming 7 residents joined the pathway. The program continues, and the current cohort of trainees have received training in clinical trials design andworked with dedicated mentor(s) regarding clinical trial ideas; their studies are currently accruing patients. ConclusionsThis pilot program has been viewed by trainees and mentors as successful; it highlights how a structured approach meets a clear need within RO training. We envision the creation of a national platform to increase access, whereby programs adopt this clinical trialist educational pathway, which ultimately leads to the development of a robust clinical trial community with communal resources. We hope that this not only improves and provides educational initiatives to all trainees but also initiates further collaboration.

Increasing Power in Phase III Oncology Trials With Multivariable Regression: An Empirical Assessment of 535 Primary End Point Analyses.

A previous study demonstrated that power against the (unobserved) true effect for the primary end point (PEP) of most phase III oncology trials is low, suggesting an increased risk of false-negative findings in the field of late-phase oncology. Fitting models with prognostic covariates is a potential solution to improve power; however, the extent to which trials leverage this approach, and its impact on trial interpretation at scale, is unknown. To that end, we hypothesized that phase III trials using multivariable PEP analyses are more likely to demonstrate superiority versus trials with univariable analyses. PEP analyses were reviewed from trials registered on ClinicalTrials.gov. Adjusted odds ratios (aORs) were calculated by logistic regressions. Of the 535 trials enrolling 454,824 patients, 69% (n = 368) used a multivariable PEP analysis. Trials with multivariable PEP analyses were more likely to demonstrate PEP superiority (57% [209 of 368] v 42% [70 of 167]; aOR, 1.78 [95% CI, 1.18 to 2.72]; P = .007). Among trials with a multivariable PEP model, 16 conditioned on covariates and 352 stratified by covariates. However, 108 (35%) of 312 trials with stratified analyses lost power by categorizing a continuous variable, which was especially common among immunotherapy trials (aOR, 2.45 [95% CI, 1.23 to 4.92]; P = .01). Trials increasing power by fitting multivariable models were more likely to demonstrate PEP superiority than trials with unadjusted analysis. Underutilization of conditioning models and empirical power loss associated with covariate categorization required by stratification were identified as barriers to power gains. These findings underscore the opportunity to increase power in phase III trials with conventional methodology and improve patient access to effective novel therapies.