Oncology Research最新文献

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with high recurrence rates and prevalent resistance to therapeutic interventions. Tumor behavior is largely dependent on the tumor microenvironment (TME) that includes immune cells, stromal components, cancer-associated fibroblasts (CAFs), the extracellular matrix (ECM), and an associated cytokine network. In this review, we examine principal mechanisms of the tumorigenic transformation, encompassing immune checkpoint disruption, therapy resistance mediated through CAFs, the contribution of hypoxic niches, and several metabolic dependencies that hold potential as future targets. Novel therapeutics developed and/or repurposed, such as immune checkpoint inhibitors (ICIs), TME modulation therapeutics, CAF reprogramming, hypoxia targeting agents, and ECM remodeling, aim to overcome TME-mediated resistance. We also examine the rationale and progress of integrating TME-targeted therapies with other treatment modalities. By identifying actionable, molecular targets within the HNSCC TME, this review presents a translational perspective for implementing TME modulation in personalized treatment. The challenges comprise TME heterogeneity, a paucity of predictive biomarkers, and a translational gap between pre-clinical and clinical practice. Future studies must be aimed at proper stratification of patients, optimization of combination treatment, and cost-effectiveness analysis of TME-modifying therapies to enable personalized medicine in HNSCC treatment.

Cancer immunotherapy has long been established as an important treatment option for cancers. In particular, Immune Checkpoint Inhibitor (ICI) has been reported to be effective against various gastrointestinal cancers (esophageal cancer, gastric cancer, colorectal cancer); however, the treatment phase in which ICI should be used and how it should be incorporated into the treatment strategy vary depending on the cancer type being treated. Multiple clinical trials and basic research on ICIs are currently underway, and new insights from these results will continue to change the clinical treatment strategy of gastrointestinal cancers. While it is desirable to have an increasing number of treatment strategy options for gastrointestinal cancers, it is necessary to organize increasingly complex treatments and select more appropriate ICI-based treatments. In addition, as gastrointestinal cancers are being controlled through multidisciplinary treatment using ICI-based treatment, local control by conversion surgery is becoming an important treatment option. We may soon see an era in which gastrointestinal cancers can be systematically controlled with ICI-based treatment, while difficult-to-control lesions can be removed by conversion surgery. In this review, we summarize the evidence of ICI-based treatment for gastrointestinal cancers and provide an overview of the treatment strategies currently underway.

Podophyllotoxin is a well-studied natural product. Because of its unique structure and ability to inhibit cancer cells, it has been changed in different ways to find out its pharmacological properties. This paper discusses the common chemical modifications of podophyllotoxin molecules, including the C-4 and E-4 site replacements. Furthermore, its common inhibitory effects on cancer cells and antiparasitic activities, among others, are outlined by the connection between conformational changes and pharmacological activities. Importantly, Podophyllotoxin can effectively overcome the phenomenon of multidrug resistance through a dual-targeting mechanism, including inhibition of microtubule protein synthesis and topoisomerase II activity, and induces cell cycle arrest and apoptosis. Recent findings reveal its potential to modulate immune responses through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, further extending beyond its classical mechanisms. This study finally provides a systematic summary of the activity of podophyllotoxin in common cancer cells, including those in the breast, lung, and prostate.

Breast cancer is among the most prevalent cancers in females globally and has the highest mortality rate. The emergence of pharmacologic resistance in breast cancer is a significant challenge for researchers in the pursuit of effective treatment. Investigations in cancer nanotechnology have been transformed by the advancement of smart polymers, lipids, and inorganic materials. Research is now being conducted in the field of innovative nano-pharmaceutical formulations aimed at enhancing the efficacy and durability of chemotherapy. Nanotechnology-based delivery systems are beneficial for combating breast cancer due to theranostic applications, augmented drug encapsulation, decreased degradation, and minimal adverse effects. This review discusses breast cancer and its stages, various risk factors, and pathogenesis, in addition to diagnosis and treatment. Novel nanocarriers are included with the most recent findings in this area and the potential use of these nanocarriers in cancer therapy that centers on their clinical usage for improved treatment. Patents and promising clinical trial results are also explained in detail, with nanotoxicity, ethical concerns, and regulations. This study underscores the importance of treatment strategies using nanotechnology, highlighting the advancing paradigm of breast cancer care. This article examines the prospects, obstacles, and future trajectories of nanomedicines.

Background: The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma (OEC) remains controversial. Hence, the study sought to explore its value in stage I OEC patients.

Methods: Stage I OEC patients (1988-2018) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analysis was used to control confounders. Logistic regression was used to explore factors associated with adjuvant chemotherapy. Cox regression analysis and Kaplan-Meier curves were used to assess the survival benefits. Single-center clinical data and meta-analysis following PRISMA guidelines provided external validation.

Result: Adjuvant chemotherapy correlated with improved survival (Hazard Ratio (HR): 0.860, p = 0.011), as did lymphadenectomy (HR: 0.842, p < 0.001). Higher age, pathological stage, and tumor grade negatively affected survival. Chemotherapy administration associated with higher pathological stage (IB: Odds Ratio (OR) 1.565, p < 0.001; IC: OR 4.091, p < 0.001), higher grade (G2: OR 2.336, p < 0.001; G3: OR 4.563, p < 0.001), and lymphadenectomy (OR 1.148, p = 0.040). Stratification analysis showed adjuvant chemotherapy failed to improve prognosis in stage IA/IB patients regardless of grade or lymphadenectomy. For stage IC patients, chemotherapy benefited grade 1-2 or grade 3 patients without lymphadenectomy, and grade 3 patients with lymphadenectomy. Meta-analysis revealed reduced recurrence in stage IC patients (OR = 0.50, p = 0.035).

Conclusion: Adjuvant chemotherapy confers survival benefits for stage IC patients, particularly those without lymphadenectomy.

Central nervous system (CNS) tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-related mortality. Their rarity compared to adult cancers has made enrolling sufficient cases for clinical trials challenging. Consequently, pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics. This review examines key aspects of phase I pediatric oncology trials, including study design, primary outcomes, and pharmacological approaches, along with secondary considerations like clinical responses and ethical aspects. Firstly, we evaluated all phase I trial protocols focusing on pediatric CNS tumors with accessible results published in scientific databases (Pubmed, Scopus, Embase, Web of Science, and Google Scholar) from 1990 to November 2024. Secondly, we searched EudraCT and ClinicalTrials.gov on 30 November 2024 for ongoing trials. Our search yielded 60 completed phase I studies and 15 trials in progress. Dividing them by chronological order revealed that study designs and the response assessments evolved as the understanding of CNS tumor biology increased. Despite advancements improving diagnosis, management, and prognostication, mortality remains high, and morbidity persists. Notably, pediatric pharmacokinetics and pharmacodynamics differ from adults, complicating trial comparisons and dosage optimization. Future efforts should focus on large-scale clinical data collection to enhance trial efficiency.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) serve an essential role in tumor angiogenesis and have emerged as potential therapeutic targets in lung cancer. This review explores the significance of serum VEGF levels as a predictive biomarker in non-small cell lung cancer (NSCLC). The VEGF family, consisting of VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor (PlGF), engages with specific receptors, including tyrosine kinase receptors (VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilin receptors (NRP-1 and NRP-2), to promote angiogenesis and lymphangiogenesis. VEGF-A, the primary component of the VEGF family, binds to VEGFR-2 to stimulate endothelial cell proliferation and migration, while VEGF-B, VEGF-C, and VEGF-D interact with VEGFR-1 and VEGFR-3 to regulate tumor angiogenesis, lymphangiogenesis, and metastasis. The VEGF/VEGFR signaling pathway activates various downstream effectors, including phospholipase Cγ1, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), which are essential for maintaining vascular homeostasis and promoting angiogenesis. In NSCLC, elevated serum VEGF levels have been observed, and the VEGF/VEGFR axis is frequently impaired, leading to irregular blood vessel formation and metastatic spread. Despite the development of anti-VEGF therapies, their impact on lung cancer outcomes has been limited. Further research is needed to optimize the effectiveness of these treatments and elucidate the potential of serum VEGF as a predictive biomarker in NSCLC.

Background: Patients with hemato-oncological malignancies may respond insufficiently to vaccination, especially in terms of antibody titer. The antibody response depends on the type of malignancy as well as the type and timing of treatment. We intended to evaluate this using real-world data from patients of our regional hospital. This study also considers the role of immune status, including T-cell activation markers, in predicting vaccination success.

Methods: Seventeen patients of our hospital having a hematological malignancy were included in this study, including myeloma, lymphoma, as well as acute myeloid leukemia (AML) and chronic lymphoid leukemia (CLL). All patients were vaccinated against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) using Tozinameran following current recommendations. Circulating antibodies directed against the spike protein of SARS-CoV-2 were determined by a commercial immune assay. Immune status was determined from peripheral blood by flow cytometry. Both parameters were followed in fifteen patients who provided sufficient follow-up data for up to one year. Patients were categorized as responders or non-responders, and differences in diagnosis, treatment, and immune status were analyzed.

Results: Antibody response depended on both diagnosis and treatment. Active treatment directed against B-cells, such as anti-Cluster of Differentiation 20 (CD20) therapy, was associated with weak seroconversion. For CD38-as well as proteasome-directed therapies, the data suggest that responders as well as non-responders exist. Notably, low peripheral B-cell numbers and high CD3+HLADR+cell counts correlated with weak seroconversion upon vaccination.

Conclusions: We suggest that peripheral immune status can be applied as a predictive biomarker for seroconversion upon vaccinations.

Deubiquitinating enzymes (DUBs) are key enzymes capable of cleaving ubiquitin chains and synergizing with ubiquitination modifications to regulate the function of key proteins and maintain normal physiological functions. OTUDs are a key subfamily of the ovarian tumor protease (OTU) family, with important DUB activities, and include mainly OTUD1, OTUD2, OTUD3, OTUD4, OTUD5, OTUD6A, and OTUD6B. In recent years, research on OTUD proteins has been gradually emphasized, and their aberrant expression has demonstrated significant research value in many diseases, such as cancer, immune abnormalities, neurological disorders, and embryonic developmental abnormalities. Therefore, a comprehensive understanding of the regulatory mechanisms of OTUD proteins and their use as therapeutic targets for diseases is of great value. This article focuses on the role of individual OTUD proteins in cancer progression and antiviral response. Importantly, in the context of cancer, we elaborate on their deubiquitinated protein targets and summarize the signaling mechanisms by which they promote or inhibit cancer progression. In the future, targeting OTUD proteins may become a therapeutic direction for cancer, and this review may be useful for research related to OTUD proteins and cancer. At present, there is a lack of research on targeted inhibitors or activators of OTUDs. More in vivo and in vitro studies on OTUDs may contribute to the development of inhibitors or agonists targeting OTUDs. Of course, when conducting these studies, researchers also need to pay attention to the impact of OTUDs on the host's antiviral immune response.

Background: Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation, which has been linked to tumor progression and therapeutic resistance. However, the contribution of lactate metabolism and its receptor, hydroxycarboxylic acid receptor 1 (HCAR1), in ferroptosis regulation in gastric cancer (GC) remains poorly understood. Focusing specifically on its effects on cell proliferation, ferroptosis regulation, and the disruption of lactate-mediated metabolic pathways, the study aimed to clarify the role of HCAR1 in GC progression.

Methods: Bioinformatics analysis identified prognostic genes associated with ferroptosis in GC. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic potential of the predictive genes. The biological role of HCAR1 was investigated through gain and loss-of-function experiments in GC cell lines, followed by assessments of cell viability, oxidative stress indicators, gene/protein expression, and ferroptosis sensitivity under lactate stimulation or HCAR1 modulation.

Results: HCAR1 was significantly upregulated in GC tissues and linked to poor patient outcomes. Silencing HCAR1 inhibited GC cell growth and induced ferroptosis, as shown by increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), along with decreased expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Conversely, HCAR1 overexpression or exposure to extracellular lactate inhibited ferroptosis and activated antioxidant defenses. Mechanistically, lactate activation of HCAR1 increases ATP levels, which in turn inactivates AMP-activated protein kinase (AMPK). It also upregulates stearoyl-CoA desaturase 1 (SCD1) through the sterol regulatory element binding protein 1 (SREBP1) signaling pathway. Blocking HCAR1 reversed these effects and restored ferroptosis sensitivity.

Conclusion: HCAR1 mediates lactate-driven ferroptosis resistance in GC through the AMPK-SCD1 signaling pathway. Targeting the HCAR1-lactate axis may offer a promising strategy for overcoming metabolic adaptation and improving GC treatment outcomes.