Joint modeling (JM) of longitudinal and time-to-event (TTE) data is a powerful statistical technique that elucidates how temporal changes in a biomarker relate to TTE outcomes while accounting for study confounders. The growing use of next-generation sequencing (NGS) in precision oncology, particularly in capturing circulating tumor DNA (ctDNA) methylation via liquid biopsy, offers new opportunities to apply JM for patient prognostication. In this study, we used JM to analyze a prospective cohort of 251 non-small cell lung cancer patients receiving standard-of-care immune checkpoint inhibitor treatment regimens. The JM is comprised of two sub-models-a hierarchical cubic spline random effects model for the longitudinal biomarker component and a Cox proportional hazards model for the TTE outcome component. Each sub-model incorporated baseline factors of age, gender, smoking status, and cancer stage. The main objective was to establish whether the evolution of a methylation-derived tumor fraction (TF) is associated with patient outcomes. Our investigation revealed that TF is strongly associated with both real-world overall survival and real-world progression-free survival. These results enable the generation of various patient-level predictions that capture the dynamic interplay between TF and patient outcomes, offering a path toward real-time, personalized prognostication. Although validation in larger, multi-center cohorts is needed before routine adoption, this work represents an important step toward integrating dynamic predictions into serial liquid biopsy monitoring. This approach demonstrates the potential of JM to provide more nuanced and adaptive disease evolution monitoring, offering better clinical decision guidance compared to static models or imaging alone.

Breast cancer remains a major global health burden and is characterized by substantial molecular and clinical heterogeneity. In recent years, considerable progress has been made in elucidating the genetic and molecular mechanisms underlying breast cancer, particularly those associated with hereditary susceptibility. Advances in genomic and functional studies have further revealed the complex mutational landscape of breast cancer, including key alterations in tumor suppressor genes, oncogenic signaling pathways, and mutagenic processes. In addition, non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression, influencing tumor progression and therapeutic resistance. Emerging strategies, including immunotherapy, precision medicine, and nanoparticle-based drug delivery systems, have significantly expanded treatment options and improved clinical outcomes. However, challenges such as tumor heterogeneity, drug resistance, systemic toxicity, and disparities in healthcare access continue to limit the effectiveness and broad implementation of these therapies. This review provides a comprehensive overview of the molecular mechanisms of breast cancer from a hereditary perspective, with a particular focus on genetic susceptibility, ncRNAs, and emerging therapeutic strategies. Additionally, it highlights current limitations and future directions, emphasizing the need for integrative approaches that combine genomic insights, advanced technologies, and personalized medicine to improve breast cancer prevention and treatment.

Cancer and hypertension (HTN) frequently coexist, and their relationship is increasingly recognized as a clinically relevant intersection between oncology and cardiovascular medicine. However, the extent to which this association reflects shared risk factors, common biological mechanisms, or treatment-related effects remains incompletely understood. In this narrative review, we focus specifically on the cancer-HTN interface and summarize epidemiological evidence while considering the potential influence of age, obesity, metabolic syndrome, dietary patterns, and psychosocial factors. We further discuss overlapping mechanisms, including chronic inflammation, renin-angiotensin-aldosterone system activation, calcium signaling abnormalities, activation of the sympathetic nervous system, metabolic dysregulation, dysbiosis of the gut microbiota and genetic and epigenetic alterations. Particular attention is given to the bidirectional interactions between cancer therapies and HTN, as well as the heterogeneous evidence concerning potential associations between antihypertensive medications and cancer outcomes. We also summarize the clinical assessment and management of cancer therapy-related HTN, including Common Terminology Criteria for Adverse Events grading, blood pressure monitoring, cardiovascular risk assessment, and current recommendations from the European Society of Hypertension (ESH) and American Heart Association. Emerging issues, including immune checkpoint inhibitor-associated cardiovascular toxicity, the potential role of cardiac biomarkers such as troponin and natriuretic peptides, and the prognostic significance of treatment-induced HTN across different tumor types, are also discussed. Overall, the available evidence supports an important clinical interplay between cancer and HTN but does not establish a uniform causal relationship. Future prospective studies integrating tumor biology, cardiovascular risk factors, treatment exposure, and longitudinal blood pressure (BP) assessment are needed to clarify these interactions and improve individualized cardio-oncology care.

Patients with HER2-positive advanced breast cancer with liver metastases (BCLM) have poor prognosis. Study RC48-C006 is a prospective, open-label, multi-center, randomized phase 2/3 trial (ClinicalTrials.gov identifier, NCT03500380). Based on the phase 2 results, the phase 3 stage was initiated to evaluate disitamab vedotin (DV) versus lapatinib plus capecitabine (L + C) in patients with HER2-positive BCLM who were previously treated with trastuzumab and taxanes. The results from the phase 3 stage are reported in this article. A total of 104 patients were randomized at 1:1 to receive DV (53 patients) or L + C (51 patients). Progression-free survival (PFS) assessed by the blinded Independent Review Committee (BIRC) was significantly improved with DV versus with L + C (median: 9.9 vs 4.9 months; stratified hazard ratio [HR]: 0.56 [95.48% CI, 0.35-0.91]; 2-sided P = 0.01), meeting the pre-specified primary endpoint. The investigator-assessed PFS was consistent with the BIRC assessment. Prespecified subgroup analysis of PFS consistently favored DV. Similar incidences of grade ≥3 treatment-related adverse events were reported with DV versus L + C (37.7% vs 36.0%). The present findings support DV as a treatment option for HER2-positive BCLM following trastuzumab and taxane therapy.

Breast cancer, especially triple-negative breast cancer (TNBC), remains a significant clinical challenge due to limited treatment options, chemoresistance, and the toxic side effects of standard chemotherapy. Cisplatin (Cis) is commonly used but faces limitations from resistance and dose-related toxicity. Berberine chloride (BRB), a natural alkaloid derived from Berberis vulgaris, shows promising anticancer effects. This study examined the antitumor activity and chemosensitizing potential of BRB combined with Cis. We initially examined the effects of BRB and Cis on murine 4T1 breast cancer cells. The results showed that both treatments inhibited cell viability, with IC50 values around 10 µM for BRB and 2.5 µM for Cis. Subsequently, we tested the synergistic effects using the Chou-Talalay method, which indicated that most of the 16 drug combinations exhibited synergy (CI < 1). The most effective combination (IC₅₀/8) had a CI of 0.12 and a Fa of 0.8, greatly reducing cell viability compared to individual treatments. The combined BRB and Cis therapy was then tested in a BALB/c mouse xenograft model via intraperitoneal injection. Cis alone at 1 mg/kg weekly lowered tumor growth by 43.13% but caused notable systemic toxicity, including body weight loss and kidney and liver damage. BRB alone at 10 mg/kg every 2 days resulted in greater tumor suppression (61.17%) with fewer side effects. The BRB/Cis combo achieved the highest tumor growth inhibition (87.05%) and markedly reduced Cis-related toxicity, evidenced by weight recovery and improved kidney and liver biochemical markers. These results indicate that BRB enhances cisplatin's antitumor effects while decreasing systemic toxicity, positioning BRB as a promising chemosensitizer for TNBC therapy.

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor, with a median survival of approximately 15 months despite current multimodal therapies. Recent clinical observations have suggested that the intravenous anesthetic propofol may be used to examine whether anesthetic agents can affect glioblastoma behavior. Several retrospective studies reported that, in surgical settings, propofol-based total intravenous anesthesia (TIVA) is associated with reduced operative time, faster recovery, lower intraoperative blood loss, and decreased postoperative complications such as seizures and cerebral edema, benefits particularly evident in patients with low Karnofsky Performance Scores. However, current clinical evidence remains limited, and the reported effects on survival and recurrence are still inconsistent. Preclinical studies showed that propofol's antitumor potential is mediated through modulation of the PI3K/AKT-Wnt-miRNA axis, reduction of oxidative stress, regulation of immune checkpoint molecules, and restoration of temozolomide sensitivity in resistant cells. However, some reports indicate that propofol may also induce stem-like features via GABA-A receptor activation, underscoring its complex and context-dependent nature. This narrative review summarizes the current molecular and clinical evidence about propofol in GBM. Available laboratory and retrospective clinical studies indicate possible antitumor effects, but the present evidence does not support definitive clinical conclusions. Large prospective and multicenter studies are still needed to clarify the clinical role of propofol in patients with GBM.

This study aimed to develop a multifunctional nanoplatform, Rg3-Lip-CaPO₄/Quercetin (R-LCP/Q), for integrating antitumor therapy, immune modulation, and cancer pain relief.

R-LCP/Q was constructed by incorporating ginsenoside Rg3 into a lipid-coated calcium phosphate nanoplatform loaded with quercetin (Que). Its physicochemical properties, pH-responsive release, cellular uptake, antitumor activity, Ca²⁺-associated intracellular effects, immunogenic cell death (ICD), immune modulation, biodistribution, biosafety, and analgesic efficacy were evaluated in vitro and in a 4T1 breast cancer-associated pain model. The involvement of transient receptor potential vanilloid 1 (TRPV1) signalling in analgesia was further assessed using the selective TRPV1 antagonist AMG9810.

R-LCP/Q exhibited pH-responsive degradation and release of Ca²⁺, Que, and Rg3 under acidic conditions, together with enhanced cellular uptake and tumor-associated accumulation following Rg3 functionalization. R-LCP/Q induced intracellular Ca²⁺ accumulation, mitochondrial depolarization, ROS generation, and tumor-cell apoptosis; these effects were markedly attenuated by the intracellular Ca²⁺ chelator BAPTA, supporting a substantial Ca²⁺-dependent contribution to the cytotoxic response. R-LCP/Q also increased ICD-associated hallmarks and promoted dendritic cells (DCs) maturation. In vivo, R-LCP/Q suppressed tumor growth and was associated with enhanced DCs maturation, increased CD8⁺T-cell responses, a shift towards an M1-like macrophage phenotype, reduced regulatory T-cell frequencies, and decreased tumor-associated TNF-α and IL-6 levels. R-LCP/Q also alleviated mechanical and thermal hyperalgesia, accompanied by reduced TRPV1 expression in dorsal root ganglia and decreased serum substance P levels; pharmacological TRPV1 blockade with AMG9810 also produced an analgesic response. Short-term haematological, biochemical, histological, and haemocompatibility assessments indicated favourable tolerability.

R-LCP/Q provides preclinical proof of concept for a multifunctional nanotherapeutic strategy integrating tumor suppression, antitumor immune modulation, and cancer pain relief. The findings support further investigation of coordinated tumor-immune-nociceptive regulation as a therapeutic approach for cancer treatment.

Tuberculosis (TB) is an infectious disease that most commonly affects the lungs and remains among the top 10 causes of death worldwide. Isolated ovarian tuberculosis is a rare form of extrapulmonary TB that usually presents with atypical symptoms and infertility. It brings significant diagnostic challenges and may mimic ovarian malignancy.

A 23-year-old nulliparous Afghan woman underwent laparotomy for suspected ovarian adnexal masses/ovarian tumor after presenting with pelvic pain, prolonged low-grade fever, and infertility for five years following marriage. Intraoperatively, bilateral ovarian cysts were noted; subsequently, bilateral cystectomies were done. Postoperative Histopathology of surgical specimens confirmed the diagnosis of tuberculosis lesions, and the patient was referred for anti-tuberculous therapy.

Isolated ovarian tuberculosis can present as adnexal masses with elevated CA-125 and could closely mimic ovarian malignancy. This case highlights the need to consider ovarian tuberculosis in the differential diagnosis, particularly in endemic regions. It emphasizes the value of histopathological confirmation to prevent misdiagnosis and to recommend early initiation of antitubercular therapy for favorable clinical outcomes.

Digestive system tumors, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer, represent one of the most prevalent and lethal malignancy groups worldwide, with high incidence and mortality rates. Despite the continuous development of chemotherapy in cancer treatment, this traditional therapy generally suffers from insufficient tumor specificity, drug resistance and limited efficacy. Precise targeting strategies such as antibody-drug conjugates (ADCs) and peptide-drug conjugates (PDCs) combine cell-targeting delivery with potent antitumor activity and have demonstrated therapeutic potential in digestive system tumors. Compared with ADCs, PDCs offer advantages such as lower molecular weight, improved tumor penetration and reduced immunogenicity risk. Preclinical studies suggest that PDCs can enhance tumor-specific drug accumulation and reduce damage to normal tissues, which may compensate for the shortcomings of traditional chemotherapy. In this review, we systematically outline recent progress in PDC research for digestive system tumors, focusing on target selection and PDC design strategies. Representative PDCs targeting integrins, GPC3, EGFR, HER2, transferrin receptor, and VEGFR in digestive system tumors are highlighted. Based on the preclinical findings and early clinical results, we provide insights on future directions for PDC treatment in digestive system tumors.

Although inhibition of the JAK-STAT signaling pathway has shown promise in cancer therapy, the therapeutic potential of PROTAC-mediated JAK1/JAK2 degradation in bladder cancer remains to be fully explored. To improve the delivery and therapeutic efficacy of PROTAC-mediated JAK1/JAK2 degradation in bladder cancer, this study developed PPcJ, a cRGD-functionalized PLGA-PEG nanoparticle encapsulating the PROTAC-based JAK1/JAK2 degrader JAPT8.

PPcJ nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, and high-performance liquid chromatography. Flow cytometry and confocal microscopy were used to evaluate cytotoxicity, anti-tumor effect, and intracellular localization, while Western blotting assessed the expression of JAK/STAT pathway and apoptosis-related proteins. In vivo tumor-associated fluorescence, antitumor efficacy, survival, histopathology, and serum biochemical parameters were assessed in tumor-bearing mice.

PPcJ exhibited a spherical nanoscale morphology. PPcJ achieved near-plateau cellular uptake at low concentrations and partially evaded lysosomal degradation, which significantly induced apoptosis in bladder cancer cells and suppressed key components of the JAK/STAT signaling pathway. In vivo, cRGD modification enabled higher tumor-specific accumulation and prolonged retention. PPcJ inhibited tumor growth by 86.2% and prolonged mean survival from 22.4 ± 4.2 to 41.0 ± 2.2 days, without significant changes in body weight, major-organ histology, or serum AST, ALT, urea, and creatinine levels under the tested conditions.

These findings provide a preclinical proof-of-concept that the PPcJ nano-delivery system improves the delivery and antitumor performance of JAPT8. This strategy warrants further evaluation in systemic therapeutic approaches for bladder cancer.