2026年 · 第04卷第01期

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, which poses significant challenges due to its complex progression and limited curative options. Transarterial chemoembolization (TACE) is a cornerstone treatment for intermediate-stage HCC, as outlined in widely accepted clinical guidelines, including the Barcelona Clinic Liver Cancer (BCLC) framework. Over the years, TACE has evolved through technological innovations and novel therapeutic combinations designed to enhance efficacy and improve patient outcomes. Recent advancements include refined imaging techniques, innovative embolic materials, and the integration of systemic therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors. These advancements have expanded TACE’s applicability and improved its efficacy in controlling tumor progression and prolonging survival in patients with unresectable HCC. Despite these advancements, challenges persist, including the optimization of treatment protocols, the management of complications, and the need for personalized treatment strategies that are tailored to diverse patient populations. This review highlights the latest progress and current understanding of TACE as a therapeutic modality for HCC. It also explores emerging trends, ongoing challenges, and the potential for novel combinations to redefine the therapeutic landscape. By synthesizing the latest evidence, this article aims to provide valuable insights for clinicians and researchers striving to improve HCC management and patient outcomes.

The pathophysiology of many ailments, including neurological, gastrointestinal, and metabolic disorders, is well known to be influenced by intestinal dysbiosis. Clinical research has provided evidence suggesting a strong correlation between dysbiosis of the gut microbiome and colorectal cancer (CRC) development. The active reprogramming of metabolic pathways to boost glycolysis, fatty acid production, lipogenesis, and glutaminolysis constitutes a major metabolic shift in cancer development, including CRC. The complex combination of different factors leads to CRC, making it an environmental disease. These factors include food and lifestyle choices, genetics and family history, age, underlying intestinal diseases, and dysbiosis of the gut microbiota. One of the primary risk factors for carcinoma development is diet, which impacts an individual’s gut microbiome. In addition to impacting CRC formation, the gut microbiome also has immunomodulatory effects, including various immunological interactions and the underlying mechanisms governing them. Microbial interactions in CRC have been extensively studied, yet numerous unresolved queries exist on how gut bacteria can influence treatment. Microbiome-driven immunotherapies, focusing on probiotics, prebiotics, and synbiotics, represent a promising therapeutic avenue. However, large-scale treatment utilization in CRC patients is limited by several issues, including variations in the microbial makeup of each patient’s gut and a lack of established methods. The study highlights the impact of several risk factors, including dysbiosis of the gut microbiome and different approaches to halting and treating CRC progression with a focus on diet changes and modulation of the gut flora. Given the foregoing, we propose that if research gaps are addressed and immunotherapy is paired with microbial interventions, microbiota-based therapeutics could potentially impede the growth of tumors and treat CRC.

Cancer, ranging from early stages to metastatic spread, is one of the leading causes of death globally. Current treatment options, including chemotherapy, radiotherapy, and targeted drugs, have limitations substantial adverse effects, the development of drug resistance, and high cost. To address these challenges, numerous studies have focused on repurposing existing drugs for anticancer therapy, with clotrimazole (CLZ) emerging as a promising candidate due to its notable anticancer activity. CLZ was first developed as an antifungal agent. Recently, significant anticancer effects have been observed making it a suitable candidate for drug repurposing. Compared with other azole-based antifungals, CLZ has shown distinct therapeutic effects on cancer cells via several pathways. Its ability to disrupt glycolysis by inhibiting phosphofructokinase (PFK) and hexokinase (HK) distinguishes it from other azoles. Furthermore, CLZ obstructs calcium homeostasis and critical survival pathways, such as extracellular signal-regulated kinase (ERK)-p65, phosphatidylinositol 3-kinase (PI3K), and mitochondrial apoptotic pathways, inhibiting tumor growth, inducing apoptosis, and attenuating metastasis. This review summarizes the potential of CLZ repurposing for cancer therapy, emphasizing its well-established safety profile and cost-effectiveness while addressing unmet clinical needs in current cancer treatment. It briefly examines in vitro and in vivo assessments to understand the mechanisms and effects of CLZ on various cancer types. Furthermore, novel strategies such as nanoformulations and combination therapies with existing chemotherapeutic drugs have been highlighted to improve therapeutic outcomes. Preclinical studies have provided promising evidence for the efficacy of CLZ in different cancers, showing tumor regression and improved responses to conventional chemotherapy or targeted therapies. Given its evident preclinical results and diverse mechanisms of action, CLZ may be considered an antineoplastic agent. Further clinical research is required to fully elucidate its anticancer potential, potentially positing it as a valuable addition to currently available cancer treatments.

Background: Immune checkpoint inhibitors combined with poly ADP-ribose polymerase (PARP) inhibitors and chemotherapy can enhance anti-tumor activity. This phase Ib clinical study was designed to evaluate the safety and efficacy of cisplatin in combination with sintilimab and niraparib in patients with advanced solid tumors. Methods: Patients with advanced solid tumors who had progressed after one or more lines of standard therapy were enrolled in the study, and received cisplatin and sintilimab on day 1 and niraparib from days 1–21 every 3 weeks for up to 4 cycles, followed by maintenance therapy with sintilimab and niraparib (the same doses and schedules as before), until disease progression, death, or intolerable toxicities. During the dose-escalation phase, patients were divided into three dose groups on the basis of a 3 + 3 dose-escalation regimen, and a dose-expansion phase was conducted based on the determined maximum tolerated dose (MTD). The primary endpoint was safety, including treatment-related adverse events (TRAEs), dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D), and the secondary endpoint was efficacy. In addition, exploratory endpoints were prespecified to analyze potential biomarkers. Results: From July 31, 2019, to July 1, 2022, a total of 26 patients were enrolled, and no DLTs were observed in the dose-escalation phase. The recommended RP2Ds of cisplatin, sintilimab, and niraparib were 60 mg/m2, 200 mg, and 100 mg every 3 weeks, respectively. All patients experienced TRAEs of varying severity, and a 19.23% (5 patients) incidence of immune-related adverse events (irAEs). With the median follow-up time of 47.9 months (95% confidence interval [CI]: 38.8–NA), objective response rate (ORR) was 26.92% (7 patients, 95% CI, 11.57–47.79), disease control rate was 57.69% (15 patients, 95% CI: 36.92–76.65), the median progression-free survival (PFS) was 3.30 months (95% CI: 2.14–4.46) and the median overall survival (OS) was 8.03 months (95% confidence interval [CI]: 3.41–12.66), with PFS rates of 26.92% (seven patients) and 11.54% (three patients) at 6 and 12 months, and OS rates of 69.23%, 34.62% and 11.54% at 6, 12 and 24 months, respectively. Patients with programmed cell death ligand 1 (PD-L1) expression ≥ 1% showed significantly longer PFS (3.93 months, P = 0.032) and OS (14.97 months, P = 0.036) compared to those with PD-L1 expression < 1%. Conclusion: The combination of cisplatin with sintilimab and niraparib showed a manageable safety profile and modest anti-tumor activity in patients with advanced solid tumors. Further validation in larger, histology-specific patients is needed to confirm clinical benefit.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer (CRPC) that is typically resistant to nearly all current therapies. In this study, single-cell RNA sequencing (scRNA-seq) and bioinformatic analyses identified Centrosomal Protein 55 (CEP55) as a critical factor in the transformation from hormone-sensitive prostate cancer (HSPC) to CRPC and, ultimately to, NEPC. Subsequent bioinformatics analyses and clinical sample validation showed that CEP55 is significantly upregulated in NEPC tissues relative to HSPC and CRPC. Furthermore, while CEP55 show no significant association with the immune microenvironment or cancer-associated fibroblasts (CAFs), our findings indicate that it directly mediates the plasticity of prostate cancer cells, thereby driving NEPC progression. Specifically, in vivo and in vitro experiments confirmed that CEP55 enhances cell proliferation, migration, invasion and the expression of NEPC biomarkers in prostate cancer. Importantly, although cisplatin is the primary treatment for NEPC clinically, CEP55 has been shown to regulate cisplatin resistance through the phosphorylation of cyclin-dependent kinase 1 (CDK1) at the tyrosine 15 (Tyr15) site. In summary, our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer, suggesting its potential as an important therapeutic target.; Cisplatin resistance; CEP55

Background: Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia (AML). This study investigated the utility of targeted next-generation sequencing (NGS) of RNA for detecting rare and unknown fusion genes in patients with AML. Methods: A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction (RT-PCR) were subjected to NGS analysis. Results: Fusion genes were detected in 21 of 72 (29.2%) patients. Among the 26 primary refractory patients, 11 (42.3%) exhibited fusion genes, whereas among the 18 relapsed patients, fusion genes were identified in five (27.8%). Notably, lysine methyltransferase 2A (KMT2A) and nucleoporin 98 (NUP98) rearrangements were enriched in refractory/relapsed patients. Additionally, recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1 (EIF4A1) were identified. The identification of additional fusion genes resulted in an approximate 20.8% (11/53) reclassification of medium-risk karyotypes to the high-risk category, thereby enhancing diagnostic accuracy. Conclusions: Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML; however, its prognostic value requires validation in prospective controlled trials.