Search Results (1,985)

Despite advances in medicine, cancer remains one of the foremost global health concerns. Conventional treatments like surgery, radiotherapy, and chemotherapy have advanced with the emergence of targeted and immunotherapy approaches. However, therapeutic resistance and relapse remain major barriers to long-term success in cancer treatment, often driven by cancer stem cells (CSCs). These rare, resilient cells can survive therapy and drive tumour regrowth, urging deeper investigation into the mechanisms underlying their persistence. CSCs express ion channels typical of excitable tissues, which, beyond electrophysiology, critically regulate CSC fate. However, the underlying regulatory mechanisms of these channels in CSCs remain largely unexplored and poorly understood. Nevertheless, the therapeutic potential of targeting CSC ion channels is immense, as it offers a powerful strategy to disrupt vital signalling pathways involved in numerous pathological conditions. In this review, we explore the diverse repertoire of ion channels expressed in CSCs and highlight recent mechanistic insights into how these channels modulate CSC behaviours, dynamics, and functions. We present a concise overview of ion channel-mediated CSC regulation, emphasizing their potential as novel diagnostic markers and therapeutic targets, and identifying key areas for future research. Full article

Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this context, cancer vaccines have emerged as a promising immunotherapeutic strategy. By activating the host immune system to eliminate tumor cells, cancer vaccines offer high specificity, low toxicity, and the potential to induce long-lasting immune memory. These advantages have positioned them as a focal point in cancer immunotherapy research. This paper provides a comprehensive overview of recent clinical advances in lung cancer vaccines, discusses the major challenges impeding their clinical application, and explores potential strategies to overcome these barriers. Full article

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Tumor treatments have substantially advanced through various approaches, including chemotherapy, radiotherapy, immunotherapy, and gene therapy. However, efficient treatment necessitates overcoming physiological barriers that impede the delivery of therapeutic agents to target sites. Drug delivery systems (DDSs) are a prominent research area, particularly in tumor therapy. This review provides a comprehensive overview of hydrogel-based DDSs for tumor treatment, focusing on the strategies and designs of DDSs based on the unique pathophysiological characteristics of tumors. The design and preparation of hydrogel systems for DDSs are summarized and highlighted. The challenges and opportunities for translating hydrogel-based DDSs into clinical applications are discussed. Full article

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of tumors with a complex molecular profile. Despite therapeutic advances, patient prognosis remains poor, emphasizing the need for more effective treatment strategies. Traditional chemotherapy, with cisplatin and 5-fluorouracil (5-FU), remains the gold standard but is limited by toxicity and tumor resistance. Immunotherapy, particularly immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and its ligand (PD-L1), has improved overall survival, especially in patients with high PD-L1 expression. In parallel, targeted therapies such as poly (ADP-ribose) polymerase 1 (PARP1) inhibitors—which impair DNA repair and increase replication stress—have shown promising activity in HNSCC. Cyclin-dependent kinase (CDK) inhibitors are also under investigation due to their potential to correct dysregulated cell cycle control, a hallmark of HNSCC. This review aims to summarize current and emerging pharmacotherapies for HNSCC, focusing on chemotherapy, immunotherapy, and PARP and CDK inhibitors. It also discusses the evolving role of targeted therapies in improving clinical outcomes. Future research directions include combination therapies, nanotechnology-based delivery systems to enhance treatment specificity, and the development of diagnostic tools such as PARP1-targeted imaging to better guide personalized treatment approaches. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article

Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, or a combination of these treatments. Emerging modalities within immunotherapy are anticipated to extend the results with conventional therapy by stimulating the patient’s own intrinsic potential for tumor-specific immunologic rejection. Combination regimens of chemotherapy and tumor-infiltrating lymphocyte (TIL) therapy in advanced colorectal cancer and pancreatic cancer, autologous monocyte therapy in advanced gastric cancer, and CAR-T therapy trained against GI-selective tumor antigens such as carcinoembryonic antigen are currently being studied. Clinical trials are underway to study the combination of various chemotherapeutic agents along with immunotherapy in the management of cholangiocarcinoma, hepatocellular carcinoma, and esophageal cancer. Alternative therapies are needed based on the tumor immune microenvironment, which can lead to a personalized approach to treatment. In this review, we discuss the current status of various modalities of immunotherapy in common GI malignancies, along with their mechanisms of immune activation and cancer suppression. We will also discuss the use of immunotherapy in less common solid GI malignancies and touch on recent advancements and clinical trials. Full article

Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in tumor biology, patient factors, and institutional practices. Methods: This review synthesizes current evidence on prognostic factors influencing CRLM management, encompassing clinical (e.g., tumor burden, anatomic distribution, timing of metastases), biological (e.g., CEA levels, inflammatory markers), and molecular (e.g., RAS/BRAF mutations, MSI status, HER2 alterations) determinants. Results: Key findings highlight the critical role of molecular profiling in guiding therapeutic decisions, with RAS/BRAF mutations predicting resistance to anti-EGFR therapies and MSI-H status indicating potential responsiveness to immunotherapy. Emerging tools like circulating tumor DNA (ctDNA) and radiomics offer promise for dynamic risk stratification and early recurrence detection, while the gut microbiome is increasingly recognized as a modulator of treatment response. Conclusions: Despite advancements, challenges persist in standardizing resectability criteria and integrating multidisciplinary approaches. Current guidelines (NCCN, ESMO, ASCO) emphasize personalized strategies but lack granularity in terms of incorporating novel biomarkers. This exhaustive review underscores the imperative for the development of a unified, biomarker-integrated framework to refine CRLM management and improve long-term outcomes. Full article

Theranostic materials, which combine therapeutic and diagnostic capabilities, represent a promising advancement in cancer treatment by improving both the precision and personalization of therapies. Recently, metal peroxides (MePOs) have attracted significant interest from researchers for their potential use in both cancer diagnosis and therapy. This review provides an overview of recent developments in the application of MePOs for innovative cancer treatment strategies. The unique properties of MePOs, such as oxygen generation, are highlighted for their potential to improve therapeutic outcomes, especially in hypoxic tumor microenvironments. Initially, methods for MePO synthesis are briefly discussed, including hydrolyzation–precipitation, reversed-phase microemulsion, and sonochemical techniques, emphasizing the role of surfactants in regulating the particle size and enhancing bioactivity. Next, we discuss the main therapeutic approaches where MePOs have shown promise. These applications include chemotherapy, photodynamic therapy (PDT), immunotherapy, and radiation therapy. Overall, we focus on integrating MePOs into theranostic platforms to enhance cancer treatment and enable diagnostic imaging for improved clinical outcomes. Finally, we discuss potential future research directions that could lead to clinical translation and the development of advanced medicines. Full article

Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, and endocrine therapy, depending on the disease subtype and the risk of recurrence. Moreover, patients with BC and germline mutations in the breast cancer genes 1 or 2 (BRCA1/BRCA2), (gBRCAm), who are typically young women, often require more aggressive therapeutic interventions. These mutations present unique characteristics that necessitate a distinct treatment approach, potentially influencing the side effect profiles of patients with BC. Regardless of the clear benefit observed with these treatments in terms of reduced recurrence and mortality rates, long-term, treatment-related adverse events occur that negatively affect the health-related quality of life (HRQoL) of BC survivors. Thus, long-term adverse events need to be factored into the treatment decision algorithm of patients with early BC (eBC). Physical, functional, emotional, and psychosocial adverse events can occur and represent a significant concern and a challenge for clinicians, patients, and their families. This review article provides an overview of the various long-term adverse events that patients with eBC may experience, including their associated risk factors, as well as management and prevention strategies. We also explore the evidence of the long-term impact of treatment on the HRQoL of patients with gBRCAm. By providing a comprehensive overview of current evidence and recommendations regarding patients’ HRQoL, we aim to equip clinicians with scientific and clinical knowledge and provide guidance to optimize care and improve long-term outcomes. Full article

Myxoma virus (MYXV), a rabbit-specific poxvirus and non-pathogenic in humans and mice, is an excellent candidate oncolytic virus for cancer therapy. MYXV also has immunotherapeutic benefits. In ovarian cancer (OC), immunosuppressive tumor-associated macrophages (TAMs) are key to inhibiting antitumor immunity while hindering therapeutic benefit by chemotherapy and dendritic cell (DC) vaccine. Because MYXV favors binding/entry of macrophages/monocytes, we examined the therapeutic potential of MYXV against TAMs. We found previously that a replication-defective MYXV with targeted deletion of an essential gene, M062R, designated ΔM062R MYXV, activated both the host DNA sensing pathway and the SAMD9 pathway. Treatment with ΔM062R confers therapeutic benefit comparable to that of wild-type replicating MYXV in preclinical models. Here we found that ΔM062R MYXV, when integrated with cisplatin and DC immunotherapy, further improved treatment benefit, likely through promoting tumor antigen-specific T cell function. Moreover, we also tested ΔM062R MYXV in targeting human immunosuppressive TAMs from OC patient ascites in a co-culture system. We found that ΔM062R treatment subverted the immunosuppressive properties of TAMs and elevated the avidity of cytokine production in tumor antigen-specific CD4⁺ T cells. Overall, ΔM062R presents a promising immunotherapeutic platform as a beneficial adjuvant to chemotherapy and DC vaccine. Full article

Background/Objectives: Most patients with non-small cell lung cancer (NSCLC) receive chemo- and/or immunotherapy, which can be associated with adverse events including fatigue. Affected patients may not be able to receive the complete chemo- and/or immunotherapy as planned. In this context, patients may benefit from maintaining their physical activity, which can be challenging. An app reminding patients to perform a certain number of steps may have a positive effect on physical activity during chemo- and/or immunotherapy. Such an app is under development and will be tested in a prospective trial. The current APACHIE-01 study (NCT06993896) is required for proper sample size calculation and design of the planned trial. Methods: The main goal of the APACHIE-01 study is to evaluate patterns and predictors of physical activity during chemo- and/or immunotherapy for locally advanced or metastatic NSCLC. The primary endpoint is the assessment of the mean number of steps per week during the first three cycles of chemo- and/or immunotherapy for lung cancer. The baseline value is represented by the mean number of steps during the last week prior to chemotherapy and/or immunotherapy. Secondary endpoints include associations between mean number of steps per week and a pain score, a distress score, and a fatigue score. The recruitment of the required 38 patients should be completed within 4 months and the treatment period will be 9–10 weeks (three cycles of chemo- and/or immunotherapy), resulting in a total running time of approximately 6 months. The APACHIE-01 study will contribute to the optimal design of a subsequent prospective trial. Full article

Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable prognosis compared to urothelial carcinoma of the bladder. Current treatment strategies for UTUC are largely derived from bladder cancer studies, underscoring the need for UTUC-directed research. This review provides a comprehensive overview of UTUC, encompassing diagnostic approaches, systemic and intraluminal therapies, surgical management, and future directions. Methods: A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC. Results: Neoadjuvant cisplatin-based chemotherapy is increasingly preferred in UTUC due to the risk of postoperative renal impairment that may preclude adjuvant cisplatin use. Surgical management includes kidney-sparing approaches and radical nephroureterectomy (RNU), with selection guided by tumor risk and patient comorbidities. While endoscopic management (EM) preserves renal function, it carries a higher recurrence and surveillance burden; RNU remains standard for high-risk cases. Systemic therapy for advanced and metastatic UTUC mirrors that of bladder urothelial carcinoma. Enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy over chemotherapy in the EV-302 trial, with improved response rate, progression-free survival, and overall survival across subgroups, including UTUC. For patients ineligible for EV, the CheckMate-901 study supported first-line chemoimmunotherapy with gemcitabine, cisplatin, and nivolumab. Further systemic therapy strategies include maintenance avelumab post-chemotherapy (JAVELIN Bladder 100), targeted therapies such as erdafitinib (THOR trial), and trastuzumab deruxtecan (DESTINY-PanTumor02) in FGFR2/3-altered and HER2-positive disease, respectively. Conclusions: Historically, the therapeutic landscape of UTUC has been extrapolated from bladder cancer; however, ongoing research specific to UTUC is deriving more precise regimens involving the use of immune checkpoint inhibitors, antibody–drug conjugates, and biomarker-driven therapies. Full article

Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article