Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, with its pathogenesis primarily linked to activating mutations in the KIT or platelet derived growth factor receptor alpha (PDGFRA) genes. Surgical resection remains the standard curative treatment for localized GIST; however, ~50% of patients eventually develop recurrence or metastasis. Since the introduction of imatinib in the early 21st century, the management of metastatic GIST has shifted from solely surgical intervention to a systemic, chronic disease management model centered on tyrosine kinase inhibitors (TKIs). However, during the course of treatment, most patients develop drug resistance. Despite the transformative impact of TKIs, some critical clinical challenges remain unresolved. Intratumoral heterogeneity, in particular, poses a significant obstacle, as tumors often comprise diverse populations of cells with varying genetic and molecular profiles. This diversity means that while some subclones may initially respond well to TKI therapy, others harboring inherent or acquired resistance mutations can continue to proliferate, ultimately leading to treatment failure. Additionally, the limited durability of TKIs responses, even in tumors initially sensitive to treatment, remains a pressing concern. Moreover, the lack of curative systemic options for advanced GIST, along with adverse drug reactions, underscores the unmet needs within this patient population. These challenges underscore the necessity of this review, which discusses current standard drug treatment strategies for advanced GIST, including sequential TKIs therapy and investigations into mechanisms of drug resistance. Finally, the review explores precise and actionable future directions for GIST drug development and clinical management, including mutation-stratified therapeutic sequencing, rational TKI-based combination regimens, and circulating tumor DNA (ctDNA)-guided real-time treatment monitoring and resistance surveillance.

Previous research has demonstrated the effectiveness of lenvatinib and programmed death-1 (PD-1) blockades in the treatment of sarcoma. However, there is limited information regarding the efficacy and safety of combining lenvatinib with PD-1 blockades as a re-challenge therapy in patients with metastatic soft tissue sarcoma (STS) following prior treatment failure with tyrosine kinase inhibitors (TKIs).

This study aimed to develop a synergistic photodynamic therapy/sonodynamic therapy (PDT/SDT) system that utilises novel NBDPBr nanoparticles (NPs). These NBDPBr NPs are composed of the aza-boron-dipyrromethene (Aza-BODIPY) dye NBDPBr, which is encapsulated in amphiphilic polymer F-127 (Pluronic®). The system is intended for the treatment of triple-negative breast cancer (TNBC), and simultaneously establishes a multimodal imaging platform for real-time monitoring of the therapeutic effect.

breast cancer remains a significant global health burden, with chemotherapy serving as a cornerstone of treatment. However, chemotherapy is associated with a high symptom burden, adversely impacting patients' quality of life. This study assessed the prevalence, severity, and impact of symptom burden among breast cancer patients undergoing chemotherapy in Delta State, Nigeria.

Lipoma is a common, benign soft tissue neoplasm consisting of mature adipocytes. Other variants exist, notably angiomyxolipoma, also referred to as vascular myxolipoma, which is an exceedingly rare benign lipomatous tumor characterized by the intimate admixture of three components: mature adipose tissue, paucicellular myxoid stroma, and a prominent vascular network. We present the case of a 55-year-old female patient who presented with a palatal swelling. Histopathological examination after surgical excision revealed an angiomyxolipoma. No abnormalities were noted after one year. Angiomyxolipoma of the oral cavity is an exceptionally rare benign neoplasm, with only a handful of well-documented cases involving the buccal mucosa, floor of mouth, tongue, and lip. Despite its rarity, recognition is important because the lesion can closely mimic other lipomatous or myxoid tumors, including malignant entities such as myxoid liposarcoma.

Protein S-palmitoylation is a highly conserved posttranslational lipid modification that occurs on cysteine residues and critically influences protein maturation, subcellular localization, trafficking, and stability. Owing to its unique reversibility and dynamic nature, S-palmitoylation plays a pivotal role in cancer. This review comprehensively summarized the expression profiles and distribution of key cancer-related S-palmitoylation enzymes in recent years. Importantly, we highlight the specific mechanisms by which the dual states of palmitoylation and depalmitoylation function as a dynamic regulatory axis during the transformation of cancer cells into cancer stem cells and during the transition from a normal tissue environment to a tumor microenvironment. Furthermore, we discussed emerging therapeutic strategies targeting S-palmitoylation, including the development of specific inhibitors and competitive blockade of substrate-binding sites, which offer additional insights into the translational potential of S-palmitoylation as a therapeutic target for cancer.

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Although the transcription-export (TREX) complex plays a central role in RNA maturation and nuclear export, the clinical and biological relevance of individual THO Complex Subunit (including THOC1, THOC2, THOC3, THOC5, THOC6, and THOC7) in LUAD is not well defined. We performed integrative analyses combining bulk transcriptomics from TCGA/GTEx and independent GEO cohorts, survival modeling, DNA methylation profiling, protein-level annotation from public resources, protein-protein interaction network analysis, immune infiltration estimation (TIMER), and single-cell RNA sequencing (scRNA-seq) to evaluate the relevance of THOC3 and THOC7 in LUAD. Across TCGA and external GEO validation datasets, THOC3 and THOC7 were consistently upregulated in LUAD and associated with poorer overall and disease-free survival, whereas other THO complex members showed weaker or inconsistent associations. Given these comparatively consistent and reproducible signals, we therefore prioritized THOC3 and THOC7 for downstream multi-layer analyses. Epigenetic profiling and interaction network analyses placed both genes within conserved RNA processing and export programs linked to genome maintenance pathways. Single-cell transcriptomic analysis provided additional resolution, demonstrating predominant enrichment of THOC3 and THOC7 in malignant epithelial clusters, with THOC3 aligning with transcriptional programs associated with DNA replication and repair, and THOC7 with proliferative and checkpoint-related states. Notably, expression of both genes was also detectable in myeloid and neutrophil subsets, and THOC7 expression remained elevated in recurrent LUAD samples, indicating association with aggressive and treatment-resistant disease states. Collectively, by integrating bulk, single-cell, epigenetic, and immune profiling across multiple independent cohorts, this study identifies THOC3 and THOC7 as reproducible molecular correlates of aggressive LUAD phenotypes. These highlight dysregulated RNA export programs as potential biomarkers of poor prognosis and motivate future functional studies to assess RNA export dependencies in LUAD.

To evaluate the short- to intermediate-term radiological evolution of ablation zones using contrast-enhanced MRI and to assess clinically relevant outcomes following irreversible electroporation (IRE) and radiofrequency ablation (RFA) in patients with liver tumors.

Increasing evidence indicates that tumor cellular senescence can impair antitumor immunity and promote skin cutaneous melanoma (SKCM) progression. However, effective methods for assessing tumor cellular senescent status and tumor immune microenvironment (TIME) status remain lacking. This study intends to establish a novel Senescence-TIME Risk Score (STIRS) based on senescence and TIME related genes to predict prognosis and immunotherapy responsiveness in SKCM patients, thereby providing new strategies for current clinical personalized treatment.

Efferocytosis plays a critical role in clearing apoptotic tumor cells and suppressing inflammation in hepatocellular carcinoma (HCC). This study aimed to identify efferocytosis-related genes (ERGs) with prognostic value and develop a predictive model for HCC outcomes.

Colorectal cancer (CRC) is one of the most prevalent and deadly gastrointestinal malignancies worldwide. Lenvatinib, a multi-tyrosine kinase inhibitor, has shown limited clinical benefit as a monotherapy for CRC. Therefore, combining lenvatinib with N-butylidenephthalide (BP), a known anticancer and adjuvant agent, has been explored to enhance therapeutic outcomes. This study investigates the effects of lenvatinib and BP, individually and in combination, on HCT15 and HCT116 CRC cell lines.

The ZZ-type zinc-finger family has emerged as an important regulator of tumorigenesis; however, its roles in renal cell carcinoma (RCC) susceptibility and prognosis are largely unexplored. This study aimed to systematically evaluate the genetic variants within this gene family to identify novel risk drivers and elucidate their downstream pathogenic networks. A total of 148 single-nucleotide polymorphisms (SNPs) were genotyped across 17 ZZ-type zinc finger genes in a cohort of 630 Taiwanese participants (312 patients with RCC and 318 healthy controls). The results were validated using pooled transcriptomic analysis of 18 independent datasets. Weighted gene co-expression network analysis (WGCNA) was used to construct tumor-specific networks and identify key driver genes. The Asian-specific variant of KCMF1 rs146409312 emerged as a significant susceptibility locus. The minor A allele conferred a 3.38-fold increased risk of RCC (adjusted odds ratio = 3.22, 95% confidence interval = 1.57-6.58, p = 0.001). KCMF1 was consistently upregulated in tumor tissues and was associated with poor patient survival. WGCNA identified a clinically relevant KCMF1-associated gene module enriched in ribosomal biogenesis and MYC target signaling. Within this network, SNRPD2 was identified as a critical hub gene, and its overexpression was strongly correlated with advanced tumor grade, stage, and reduced overall survival (p < 0.001). In conclusion, KCMF1 rs146409312 was identified as a potent, population-specific risk factor for RCC. A pathogenic KCMF1-driven network converging on SNRPD2 was delineated, offering novel insights into RCC etiology and highlighting potential biomarkers for prognostic stratification.

Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed malignancies and exhibits a high mortality rate. Patchouli alcohol (PA) is a tricyclic sesquiterpene derived from Pogostemon cablin, and the present study evaluated the antihepatoma capacity of PA and described a potential strategy for its combination with sorafenib (SOR) in vitro and in vivo. The anticancer potential of PA against HCC was evaluated using the MTT assay, flow cytometry, western blotting, DCF-DA and JC-1 staining, TUNEL assay, immunofluorescence and immunohistochemistry staining, and migration and invasion assays. The results indicated that PA suppressed HCC growth by inducing reactive oxygen species (ROS) generation, mitochondrial membrane potential imbalance, and DNA damage, ultimately resulting in cell cycle arrest and apoptosis via the activation of p53/p21 and also extrinsic (Fas/FasL/caspase-8), intrinsic (Bax/Bcl2/caspase-9), and caspase-independent pathways. The combination of PA with SOR exhibited synergistic effects, exerted survival benefits, and improved the lifespan of mice at well-tolerated doses. Furthermore, PA targets the androgen receptor (AR) to inhibit dihydrotestosterone-induced (DHT)-induced cell proliferation, AR translocation to the nucleus, and downstream gene expression during HCC growth. On the whole, PA alone or in combination with SOR exhibited markedly improved therapeutic efficacy in HCC by blocking AR-mediated and multiple other signaling pathways. Therefore, this study provides an experimental basis for the evaluation of PA as an alternative drug (alone or in combination) for the treatment of HCC.

Acute myeloid leukemia (AML) harboring IDH1 mutations presents unique metabolic vulnerabilities that remain incompletely addressed by current targeted therapies. In this study, we demonstrate that IDH1-mutant AML cells are markedly more sensitive to cuproptosis induced by the copper ionophore elesclomol (ES), compared to their wild-type counterparts. While ES impairs mitochondrial function in both cell types, transcriptomic profiling reveals that ES treatment induces a global downregulation of lipid metabolism pathways. Functional assays further show that IDH1-mutant cells rely more heavily on exogenous fatty acids and exhibit impaired de novo lipogenesis. Under lipid-deprived conditions, ES-induced cytotoxicity is significantly enhanced, suggesting a synthetic-lethal interaction between cuproptosis and fatty acid metabolic deficiency. In vivo experiments confirm that ES more effectively suppresses tumor growth in IDH1-mutant xenografts. These findings uncover a copper-dependent metabolic vulnerability and provide a rationale for exploiting cuproptosis as a therapeutic strategy in IDH1-mutant AML.

Oral cancer ranks as the fourth most common cancer among men in Taiwan and the ninth most common cancer among men worldwide. Nesfatin-1, an adipokine derived from the precursor NUCB2 gene, was originally discovered in hypothalamic neurons. The connections among lifestyle factors that promote cancer, NUCB2 polymorphisms, and oral cancer are still not well understood. We examined the association of four NUCB2 gene polymorphisms (rs1330, rs214101, rs757081, and rs10766383) and clinicopathological characteristics with oral cancer in Taiwanese men compared with healthy controls. According to our data, in patients aged ≥60 years, specific NUCB2 genotypes were significantly associated with more aggressive disease features. Compared with the wild-type C/C genotype, carriage of at least one polymorphic allele (T allele at rs1330 or G allele at rs757081) was correlated with an elevated risk of progression to stage III/IV disease. Furthermore, the GA/AA genotypes at rs214101 and the TG/GG genotypes at rs10766383 were associated with elevated risks of both advanced-stage (III/IV) disease and lymph node metastasis. Our findings suggest that NUCB2 SNPs may play a pivotal role in oral cancer progression and metastatic potential, particularly in older patients.

Background/Aims: Globally, colorectal cancer ranks third in causing 900,000 deaths annually. Some patients undergoing chemotherapy develop resistance, leading to metastasis. We investigated CHGA and UCHL1 proteins correlate with lymph node metastasis (J Cell Mol Med. 2023;27:2004-2020). This study aimed to analyze the relationship of CHGA and UCHL1 with the epithelial-mesenchymal transition (EMT) and the Rho/ERK/NFκB signaling pathway in OXA-resistant CRC cells.

Oral tongue cancer is an aggressive malignancy and represents the most common subsite of head and neck cancer. The long non-coding RNA myocardial infarction associated transcript (MIAT) has been implicated in the development and progression of several cancers. This study aimed to investigate the association between MIAT single-nucleotide polymorphisms (SNPs) and oral cancer susceptibility as well as related clinicopathological characteristics. In this study, MIAT SNPs (rs4274, rs1061540, and rs1894720) were genotyped using real-time polymerase chain reaction in 1,194 controls and 397 male patients with tongue cancer. A significant association was observed between the MIAT rs4274 AA genotype and the occurrence of tongue cancer compared with controls (p = 0.018). Among the patients, carriers of the rs4274 A allele exhibited a higher likelihood of developing moderately or poorly differentiated tumors [OR (95% CI) = 2.246 (1.217-4.147); p = 0.001]. Betel-quid chewers and smokers carrying the A allele showed similarly elevated risks for poor tumor differentiation. Bioinformatic analyses further indicated that the rs4274 A allele is associated with increased MIAT expression, and higher MIAT levels correlated with higher tumor grade. In conclusion, the MIAT rs4274 A allele is linked to poorer tumor differentiation, particularly among betel-quid chewers and smokers, and elevated MIAT expression supports its potential as a biomarker of tumor aggressiveness.

The intratumoral microbiota, as an important component of the tumor microenvironment (TME), impact tumor progression by regulating the arginine-ornithine metabolic axis. It has become a new frontier in tumor research. Arginine is a crucial amino acid in TME, and its metabolites, ornithine and polyamines, directly promote tumor proliferation and induce immunosuppression. Intratumoral microbiota mainly exert their effects through two direct pathways: 1) arginine depletion, such as Streptococcus in gastric cancer. Specific intratumoral microbiota highly express arginine deiminase (ADI) or arginase (Arg) to consume arginine in the TME, leading to T cell dysfunction and enhancing immunosuppressive cells. 2) Ornithine/polyamines supplement, such as fusobacteria in esophageal cancer produce putrescine. The microbiota converts arginine into ornithine, which is then synthesized into polyamines, directly stimulating tumor cell proliferation and reshaping the immunosuppressive TME. Additionally, the metabolic products from the microbiota like short-chain fatty acids (SCFAs) and indole substances, can amplify these effects through signaling pathways including G protein-coupled receptor 43 (GPR43) and aryl hydrocarbon receptors (AHR). The regulation of intratumoral microbiota-arginine metabolism axis has a "double-edged sword" characteristic, relying on the metabolic dependence of the different tumors, which provides a basis for precise treatment. Furthermore, strategies targeting the axis present great potential, including Arg1 inhibitors (CB-1158) in combination with immunotherapy, engineered probiotics to supply arginine and inhibit polyamine synthesis in situ within the TME. These advancements also indicate there is enormous progress from exploring the intratumoral microbiota-metabolism interaction to developing novel tumor microecological therapies.

Differentiated thyroid cancer (DTC) is the most commonly diagnosed endocrine cancer. Diagnosis of DTC metastases is possible with the use of ultrasound, RAI scintigraphy, [18F]FDG PET/CT, or contrast-enhanced CT; however, the use of iodine contrast factors (ICF) delays potential RAI treatment. Dual energy computed tomography (DECT) is a variant of computed tomography that enables the detection and calculation of iodine concentration in tissues. The study aimed to evaluate the potential use of non-contrast DECT in diagnosing DTC metastases.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a diverse group of tumors, ranging from well-differentiated neuroendocrine tumors to poorly differentiated neuroendocrine carcinomas. Current biomarkers for GEP-NENs are weak and lack sufficient sensitivity and specificity, complicating diagnosis and prognosis. Alpha-fetoprotein (AFP), a well-established biomarker in other cancers, has been reported as a potentially useful biomarker also for GEP-NENs, but its clinical relevance remains unclear. This narrative review evaluates AFP's role in GEP-NENs.