Radioresistance compromises pancreatic cancer radiotherapy outcomes, making the identification of radiosensitizing strategies a critical priority. AZD5153, a novel specific Bromodomain-containing protein 4 (BRD4) inhibitor, has demonstrated efficacy in relapsed/refractory solid tumors and lymphomas. Our research focuses on investigating the effect of AZD5153 on the radiotherapy sensitivity of human pancreatic cancer cells, and its underlying mechanisms.

Cetuximab is an approved therapy for metastatic colorectal cancer (CRC) with wild-type RAS and BRAF; however, additional resistance mechanisms beyond genetic mutations remain poorly understood. Butyrate, a key metabolite produced by the gut microbiome and present in the circulatory system, has been reported to supply cellular energy and modulate the epidermal growth factor receptor (EGFR) downstream signaling pathway. However, whether butyrate affects the resistance to cetuximab is still unknown.

Advances in cancer treatment have led to improved survival rates, but challenges related to health-related quality of life (HRQoL) persist, often exacerbated by sleep disturbances. We present a pre-registered, secondary analysis of HRQoL from a trial of sleep interventions among women with early or advanced breast cancer receiving chemotherapy.

This study aimed to comprehensively investigate the anti-ovarian cancer (OC) efficacy of Yiyi Fuzi Baijiang Powder (YFBP), identify its key chemical constituents, and elucidate the underlying mechanisms of action.

The glycoengineered humanized monoclonal type II anti-CD20 antibody obinutuzumab is widely used in the treatment of patients with chronic lymphocytic leukemia (CLL), most commonly in combination with other therapeutic agents. The aim of this single-centre retrospective study was to evaluate the treatment patterns and clinical responses in patients with CLL treated with obinutuzumab-based combination regimens at the University Clinic of Hematology, Skopje. We analyzed 90 patients with CLL treated with obinutuzumab-based regimens between 2019 and 2024. Obinutuzumab was administered in combination with chlorambucil (56.6%), fludarabine-cyclophosphamide (26.6%), bendamustine (11.1%), CVP (4.4%), or venetoclax (5.5%). The treatment was given as first-line therapy in 57.7% of patients and in the relapsed/refractory setting in 42.3%. The median age at initiation of obinutuzumab-based therapy was 66.9 years. The overall response rate to obinutuzumab-based treatment was 45.5%. The median follow-up after treatment was 15.6 months. In this real-world single-centre experience, obinutuzumab-based combination regimens showed measurable clinical activity in routine practice across different treatment lines. Longer follow-up and larger patient cohorts are required to better characterize the durability of the responses and outcomes in the specific treatment subgroups.

Junctophilin 3 (JPH3) acts as a tumor suppressor in several cancers; however, the role of JPH3 in anaplastic thyroid cancer (ATC) is still unknown.

Over half of esophageal cancer (EC) cases occur in China, where paclitaxel and platinum agents have become the preferred chemotherapeutic regimen for EC patients. However, there is a clinical need for a non-platinum-based therapeutic option.

Cellular stresses regulate transcriptional readthrough, whereby RNA polymerase II elongates past a gene's polyadenylation cleavage site without RNA cleavage. Readthrough has been reported in several cancer types. Here, we use long-read sequencing of nascent RNA to quantify transcriptional readthrough in chronic myeloid leukemia (CML) cells and characterize early responses to the targeted therapeutic, imatinib. We show that the amount, length, and gene specificity of readthrough increase within 1 hour, before gene expression and alternative splicing alterations emerge. Notably, imatinib-dependent messenger RNA (mRNA) isoform changes involved "readthrough chimeras," in which exons from an upstream gene are alternatively spliced to exons in a downstream gene. Altered mRNA isoforms and chimera levels were detected in imatinib-resistant K562 cells as well as cells of patients with CML. Thus, imatinib can provoke a cascade of early changes to transcription and splicing fidelity that may lead to longer-term adjustments in gene expression, cancer cell differentiation, and the development of therapy resistance.

Talquetamab (TAL), a first-in-class bispecific antibody targeting GPRC5D and CD3, has demonstrated high efficacy in heavily pretreated relapsed and refractory multiple myeloma (RRMM), achieving response rates of approximately 70%. However, TAL is frequently associated with on-target, off-tumor oral toxicities.

Astragalus membranaceus, a Qi‑tonifying herb widely used in traditional Chinese medicine, has emerged as a promising adjuvant for female‑predominant malignancies, including breast, ovarian and cervical cancers. Its major bioactive constituents, Astragalus polysaccharides (APS) and astragalosides (AST), exert multitarget antitumor activities and are widely used as complementary agents in clinical oncology. Nevertheless, key mechanistic gaps persist, particularly regarding the crosstalk among the PI3K/Akt/mTOR, Wnt/β‑catenin, JNK/MAPK and TGF‑β/Smad pathways, as well as the subtype‑ and context‑dependent regulation of molecular effectors governing programmed cell death, epithelial‑mesenchymal transition and immune reprogramming. This uncertainty constrains biomarker discovery and the rational design of combination regimens, thereby limiting the predictability of clinical benefit. The present review systematically collates current research on the molecular mechanisms and signaling networks through which APS and AST modulate breast, ovarian and cervical cancer biology. Available data indicate that these compounds suppress tumor initiation and progression by inhibiting proliferation, inducing programmed cell death, attenuating invasion and metastasis, reshaping antitumor immunity and macrophage polarization, and potentiating chemotherapeutic efficacy while mitigating treatment‑related toxicity. Overall, these insights aim to provide a mechanistic rationale for the clinical integration of A. membranaceus as an adjuvant therapy in gynecological and breast cancers, to bridge traditional Chinese medicine with contemporary pharmacology, and to support the development of individualized, integrative therapeutic strategies for breast, ovarian and cervical cancers.

We report a case of a 79-year-old woman with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer who developed secondary aplastic anemia during treatment with the EGFR tyrosine kinase inhibitor (TKI) osimertinib. In the 23rd week of osimertinib treatment, the patient developed pancytopenia accompanied by fatty bone marrow. Discontinuation of osimertinib and initiation of treatment with cyclosporine A (100 mg/day) and eltrombopag (25 mg/day), a thrombopoietin receptor agonist, resulted in hematological recovery. Gefitinib, a first-generation EGFR-TKI, effectively suppressed the progression of lung cancer without any recurrence of pancytopenia for four months. However, rechallenge with osimertinib upon disease progression resulted in the recurrence of pancytopenia. This case suggests that osimertinib can cause severe hematological toxicity, such as aplastic anemia, possibly through an immune-mediated mechanism independent of EGFR inhibition.

Psoriasiform eruption is an uncommon cutaneous immune-related adverse event (irAE) associated with anti-PD-1 therapy, and its rapid recurrence upon switching to a different anti-PD-1 agent is a scarcely documented phenomenon. We report the case of a 59-year-old man with stage IIB lung adenocarcinoma who developed a pruritic, scaly eruption after his fourth cycle of pembrolizumab. Histopathological examination confirmed a diagnosis of grade 2 psoriasiform dermatitis according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The initial episode was resolved with systemic corticosteroids. However, upon switching anti-PD-1 therapy to tislelizumab, a similar but more widespread eruption recurred rapidly within a week. The recurrence was successfully managed with topical corticosteroid and antihistamines, and the anti-PD-1 therapy was subsequently discontinued. During the 3-year follow-up after discontinuation, the patient's skin lesions resolved completely with no recurrence, and no tumor progression was observed. The reduced latency of psoriasiform dermatitis recurrence upon anti-PD-1 inhibitor rechallenge suggests a memory T cell-driven immune response. It also highlights that such irAEs were observed with the two PD-1 inhibitors pembrolizumab and tislelizumab used in this case and can be effectively managed. In this case, tumor progression was not observed after treatment cessation, although causality cannot be inferred.

Immune checkpoint inhibitor-induced bullous pemphigoid (ICI-BP) is a rare and complex cutaneous immune-related adverse event (cirAE) that often impacts the continuation of ICI therapy. Currently, there are no prospective clinical studies addressing the optimal management of BP alongside ICI continuation, with existing evidence largely derived from case reports or series. This study systematically analyzes published case reports and series to compile evidence regarding the management of ICI-BP and ICI rechallenge, aiming to inform clinical practice.

To identify the impact of CT-defined emphysema on efficacy and immune checkpoint inhibitor-related pneumonitis (ICIP) risk among non-small cell lung cancer (NSCLC) patients who receive ICIs.

Osteosarcoma is a primary bone malignancy of adolescents and young adults with marked heterogeneity and a high metastatic propensity. Five-year survival exceeds 70% in localized disease but falls to about 20% with pulmonary metastasis or chemoresistance, and overall outcomes have plateaued for decades. Extracellular vesicles (EVs) have emerged as critical mediators of osteosarcoma progression and metastasis. EVs remodel the tumor microenvironment (TME) by promoting immune evasion, extracellular matrix reprogramming, and angiogenesis, while also facilitating invasion, epithelial-mesenchymal transition (EMT)-like plasticity, and formation of lung pre-metastatic niches through organotropic integrins and glycoproteins. Their cargo, including proteins, lipids, and nucleic acids, drives intercellular communication that sustains proliferation, migration, and therapy resistance under metabolic or hypoxic stress. Clinically, the stability of EVs in body fluids and their tumor-specific molecular signatures highlight their promise as liquid-biopsy biomarkers for early diagnosis, prognosis, and treatment monitoring. Therapeutically, EVs are being engineered as delivery vehicles for drugs or RNA therapeutics, and interventions targeting their biogenesis, cargo sorting, or uptake are under exploration. Future research should integrate single-EV multi-omics, longitudinal cohort validation, and causal perturbation models to delineate functional mechanisms. Rational strategies that modulate EV dynamics and incorporate standardized analytic pipelines may transform EVs into actionable biomarkers and therapeutic targets, offering new avenues to overcome resistance and improve clinical outcomes in osteosarcoma.

The rapid advancements in nanotechnology have provided unprecedented opportunities for the clinical translation of vitamin C (VC) in cancer therapy. Although pharmacological doses of VC exhibit potent anti-tumor activities via multiple mechanisms-including selective pro-oxidative stress induction, metabolic inhibition, epigenetic modulation, and immune function enhancement-the clinical application of VC remains significantly hindered by its inherent instability, short biological half-life, and lack of tumor-specific targeting. Recent progress in the design and synthesis of VC and its derivatives combined with advanced nanocarriers has enabled precise delivery and efficient release of VC at tumor sites. In this review, we systematically summarize recent advances in nano-formulation strategies of VC, with a detailed discussion of lipid-based nanocarriers including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles, as well as metal-based nanozyme delivery systems primarily composed of iron, copper, and manganese. These nano-systems not only significantly enhance the stability and circulation half-life of VC but also exploit tumor microenvironment-specific stimuli, such as pH, hydrogen peroxide (H2O2), and glutathione (GSH), to achieve responsive and precise drug release in cancer tissues. Notably, metal-based nanomaterials in combination with VC synergistically catalyze the Fenton reaction, markedly boosting reactive oxygen species (ROS) generation and demonstrating remarkable anti-tumor efficacy. Moreover, nanotechnology platforms have facilitated effective combination therapies involving VC with chemotherapeutic agents, photothermal catalysts, and immune agonists. Finally, this article highlights key challenges in the clinical translation of nano-formulated VC, including safety evaluation, scale-up production, and prediction of therapeutic efficacy. Future research directions in nano-drug design and exploration of synergistic mechanisms are proposed, providing theoretical guidance and practical insights for precise cancer therapy using VC-based nanomedicine.

Lung cancer is the malignant tumor with the highest incidence and lethality worldwide. Existing therapeutic modalities suffer from side effects, drug resistance, and limited efficacy, and there is an urgent need to develop safer and more effective therapeutic strategies. Curcumin (Cur) and astragaloside IV (AS) are promising natural anti-cancer agents. However, their poor aqueous solubility and low bioavailability limit their clinical efficacy. Natural cell membrane-based biomimetic drug delivery platform provides an effective strategy for efficient and targeted co-administration.

Chemotherapy, the first approach in breast cancer management, is limited owing to systemic toxicity and drug resistance. For instance, 5-fluorouracil in recommended doses cause severe side effects, highlighting the urgent necessity of finding more effective and safer combinations. Hence, this study aims to develop biocompatible natural-based nanocarriers for the co-delivery of loratadine, an antihistaminic drug along with 5-fluorouracil in order to enhance the anticancer efficacy while reducing the required dose of 5-fluorouracil.

The clinical advancement of cancer nanomedicine is significantly hindered by its limited accumulation in tumors, a key factor behind the frequent failure of nanodrugs in clinical trials. The effectiveness of these nanodrugs is closely tied to their route of administration, whether oral, transdermal, intravenous, or intracerebral, as each path presents unique physiological barriers that impede bioavailability and precise tumor targeting. Among the major causes of poor accumulation are rapid clearance by the mononuclear phagocyte system, opsonization accompanied by protein corona formation, renal filtration, and the abnormal, heterogeneous nature of tumor vasculature that restricts passive targeting via the enhanced permeability and retention (EPR) effect. In response, active targeting (AT) strategies have been widely explored, including surface modification with ligands, antibodies, or aptamers designed to bind specifically to overexpressed receptors on cancer cells or blood vessels. Despite these efforts, challenges such as the dense extracellular matrix, elevated interstitial fluid pressure, and the notable inconsistency of the EPR effect between animal models and human patients continue to limit therapeutic penetration. This review offers a systematic examination of nanodrug delivery pathways and the reasons behind their inadequate accumulation, highlighting the potential of both active targeting and combined passive-active strategies to enhance tumor-specific delivery. Overcoming these biological barriers through refined nano-design is crucial for developing the next generation of nanomedicines with improved tumor accumulation and treatment outcomes.

Colon cancer ranks as the third most common malignant tumor globally. Due to incomplete surgical resection and the multidrug resistance of tumor cells, it exhibits a high postoperative recurrence rate. Consequently, there is an urgent need to develop novel therapeutic strategies to inhibit postoperative recurrence of colon cancer.