Taxane-induced peripheral neuropathy (TIPN) affects quality of life and ability to complete cancer treatment and has limited effective interventions for prevention and treatment.

The bone marrow (BM) niche serves as a critical protective environment for leukemia cells, particularly chemo-resistant leukemia cells, and plays a central role in driving therapeutic resistance and disease relapse in acute myeloid leukemia (AML). This specialized microenvironment not only promotes leukemia cell survival, but also inhibits T cell infiltration, which serves as a major obstacle to the effectiveness of CAR-T therapy in myeloid malignancies. To overcome this limitation, we targeted Rac1 GTPase, a central regulator of cytoskeletal dynamics that controls membrane protrusion and migration, by engineering primary human T cells and CD33 CAR-T cells to express constitutively active Rac1 (Rac1V12). Our results demonstrated that active Rac1 enhanced the migration of T cells and CD33 CAR-T cells and promoted their residence in the BM in vivo. Furthermore, CD33 CAR-T cells expressing Rac1V12 displayed enhanced cytotoxicity against leukemia cells in vitro, as demonstrated by transwell migration-dependent killing assays. Crucially, these engineered CAR-T cells achieved superior robust suppression of leukemia in vivo and significantly prolonged survival in xenograft models. Mechanistically, Rac1V12 CD33 CAR-T cells in the BM demonstrated enhanced immunological memory phenotype and lower tonic signaling, a combination that promotes T cell persistence and enhances anti-tumor efficacy in vivo. Our data suggest that active Rac1-engineered CD33 CAR-T cells represent a novel strategy for targeting BM leukemia cells, with the potential to eradicate AML cells.

Real-world evidence comparing long-term safety between PD-1 and PD-L1 inhibitors is limited, and the impact of competing mortality is unclear.

Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been found to be closely associated with the initiation and progression of various tumors; however, its role in oral squamous cell carcinoma (OSCC) remains unclear. AFAP1-AS1 expression in OSCC cells was detected using qRT-PCR. The regulatory effects of AFAP1-AS1 on tumor cell proliferation, migration, and invasive capabilities were systematically evaluated through CCK-8 proliferation, colony formation, wound healing, and Transwell invasion assays. Flow cytometry was employed to quantitatively analyze its impact on cell cycle progression and apoptotic. Based on bioinformatics predictions, a dual-luciferase reporter system was utilized to validate the targeting interactions among AFAP1-AS1, miR-93-3p, and CCND1. Functional rescue experiments were conducted to elucidate the functional regulatory network among them. Furthermore, a xenograft tumor model in nude mice was employed to verify in vivo the promoting effect of AFAP1-AS1 on tumor growth. AFAP1-AS1 was significantly upregulated in OSCC cells. AFAP1-AS1 knockdown inhibited the malignant phenotypes of OSCC cells. Mechanistic studies revealed that AFAP1-AS1 could target miR-93-3p and regulate CCND1 expression, thereby influencing OSCC progression. Subcutaneous tumor model in mice further confirmed the in vivo relevance of the AFAP1-AS1/miR-93-3p/CCND1 axis. AFAP1-AS1 downregulation inhibited OSCC progression through the miR-93-3p/CCND1 axis.

Colon cancer remains one of the most prevalent and aggressive malignancies, underscoring the demand for targeted and biologically safe therapeutic strategies. Arginine deiminase (ADI) has gained increasing interest as a potential anticancer agent due to its ability to modulate cellular arginine availability and inhibit tumor progression.

The intravesical Bacillus Calmette-Guérin (BCG) immunotherapy in Bladder Cancer (BC) is the standard adjuvant therapy with challenges such as limited efficacy and recurrence. We aimed to assess the synergistic antitumor effects of melatonin and BCG in vivo.

Aggressive brain tumors such as glioblastoma (GBM) remain among the most lethal human cancers, with a median survival of only 15 months despite multimodal treatment. Their resistance arises from a triad of barriers-the blood-brain barrier (BBB), marked intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment (TME). Immunotherapeutic strategies based on natural killer (NK) and T cells, leveraging antigen-independent cytotoxicity and antigen-specific precision, respectively, offer potential breakthroughs but are often limited by chronic neuroinflammation. A key driver of TME suppression is prostaglandin E2 (PGE2), produced via the cyclooxygenase-2 (COX-2) pathway. PGE2 exerts a dual role: Intracellularly, it can promote apoptosis, whereas extracellularly, it fosters tumor progression, immune evasion, and therapeutic resistance. Through activation of EP2 and EP4 receptors, PGE2 signals via Gαs proteins to elevate cyclic adenosine monophosphate (cAMP), leading to impaired cytotoxic immunity. This signaling downregulates NK cell activating receptors (e.g., NKG2D, NKp30), induces CD8⁺ T cell exhaustion, and promotes regulatory T cell expansion. The COX-2/PGE₂ axis further mediates resistance to checkpoint inhibitors, CAR-T therapy, and chemotherapy by enhancing neuronal excitation through EP1 receptor activation in GBM. Targeting this pathway has therefore emerged as a compelling therapeutic strategy, which can restore NK and T cell function and sensitize tumors to immunotherapy. Combining PGE₂ modulation with next-generation NK/T cell approaches-including CAR-NK and CAR-T platforms-holds promise to overcome immune resistance and redefine therapeutic paradigms for GBM and other central nervous system malignancies.

Sorafenib is the first-line therapy for advanced hepatocellular carcinoma (HCC). However, acquired resistance to sorafenib remains a significant challenge. Previous studies have shown that sorafenib treatment induces the formation of truncated O-glycans in HCC cells, but the relationship between sorafenib-induced glycosylation changes and acquired therapy resistance remains unclear. Primary natural killer (NK) cells, freshly isolated from peripheral blood or following culture and expansion, expressed the glycoimmune checkpoints Siglec-7 and Siglec-9. HCC cells exhibited varying levels of Siglec-7/9 ligands on their surface. Sorafenib-resistant liver cancer cells displayed hypersialylation, leading to increased expression of surface Siglec-7/9 ligands, which conferred protection against NK cell-mediated cytotoxicity. Silencing ST3GAL1 significantly reduced Siglec-7 ligand expression on liver cancer cells, enhancing their susceptibility to NK-mediated cytotoxicity and cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) in epidermal growth factor receptor (EGFR)-expressing tumor cells. Furthermore, high ST3GAL1 expression correlated with poor clinical outcomes in patients with stage 1-2 HCC. This study highlights the critical role of ST3GAL1 in regulating Siglec-7 ligands to facilitate immune escape from NK cell cytotoxicity. Moreover, its elevated expression is associated with adverse clinical outcomes in HCC. Targeting ST3GAL1 may represent a promising strategy to enhance NK cell-mediated anti-tumor immunity in HCC.

We explored the fundamental feasibility, technical frame conditions and effectiveness of transcranial Tumor Destructive Mechanical Impulse (TMI) treatment of brain tumors.

Purpose To develop a lung-specific deformable image registration algorithm optimized for lung thermal ablation and evaluate whether three-dimensional (3D) margin assessment predicts time to local recurrence. Materials and Methods This institutional review board-approved, single-institution retrospective study evaluated patients who underwent lung thermal ablation with available pre- and postprocedural CT scans suitable for deformable registration. Images were preprocessed with segmentation of tumor, ablation zone, and lung. A four-stage deformable image registration framework was applied: (a) affine registration, (b) deformable image registration to the cropped lung, (c) lung mask-guided deformable image registration, and (d) local deformable image registration focused on the neighborhood adjacent to the ablation zone. Registrations were performed using free-form B-spline transformations with cost function masking of the ablation zone. Registration accuracy was assessed using target registration error (TRE). The 3D ablation margins were quantified using a distance-transform-based analysis of the spatial relationship between the tumor surface and ablation zone boundary. Associations between margin size and time to local recurrence were evaluated using competing-risks regression, and time-dependent receiver operating characteristic analysis was performed. Results A total of 69 patients (median age, 59 years [IQR, 50-69 years]; 38 female) with 108 ablated lung tumors were included. Mean TRE ± SD was 0.4 mm ± 0.3 and mean ablation margin was 1.6 mm ± 2.1. Larger margins were associated with longer time to local recurrence (subdistribution hazard ratio, 0.5 per millimeter increase [95% CI: 0.4, 0.6]; P < .001) and remained independently associated on multivariate analysis. Using a 2-mm margin threshold, the 2-year local recurrence rate was 3% (95% CI: 1, 8). The area under the receiver operating characteristic curve for predicting 2-year local recurrence was 0.86. Conclusion The four-step lung-optimized deformable image registration framework enabled accurate automated 3D tumor ablation margin quantification, and margin size was associated with time to local recurrence. Keywords: Ablation Techniques, Interventional-Oncology, Percutaneous, Thorax, Lung, Computer Applications-3D, Computational Studies, CT © RSNA, 2026.

Purpose To simulate an artificial intelligence (AI)-driven triaging workflow in which an AI system, using high-confidence thresholds, assesses a subset of prostate MRI examinations for clinically significant prostate cancer (csPCa), compare the assessment with stand-alone radiologists, and evaluate the number of examinations triaged by the AI to estimate potential workload reduction. Materials and Methods Data from an international AI confirmatory study (February 2022-November 2023) were used in this retrospective study. MRI examinations of 500 men with suspected csPCa from four European centers were included. Exclusion criteria were prior prostate treatment, prior csPCa, or considerable imaging artifacts. AI-triaging thresholds were calibrated on 100 examinations. The AI system assessed examinations exceeding high-specificity or high-sensitivity thresholds, with the remaining examinations deferred to radiologists. The workflow was simulated on 400 examinations, including examinations from an external site, incorporating assessments from 62 radiologists. Reference standards were histopathology and/or 3 or more years of follow-up. Sensitivity and specificity of the triaging workflow were compared with the conventional workflow using multireader, multicase analysis of variance. Results Among the 400 patients (median age, 66 years; IQR, 60-69 years) included for testing, radiologists achieved a sensitivity of 89.4% (95% CI: 85.8, 93.1) and specificity of 57.7% (95% CI: 52.3, 63.1). The AI-driven pathway maintained comparable sensitivity (89.0%; 95% CI: 85.0, 93.0; P = .36) but improved specificity by 11.5%, reaching 69.2% (95% CI: 64.4, 74.0; P < .001). The AI system triaged and diagnosed 195 of 400 (49%; 95% CI: 173, 216) examinations with sensitivity of 94.7% (95% CI: 89.5, 99.9) and specificity of 94.7% (95% CI: 90.5, 98.9). Conclusion Triaging by this AI system improved simulated diagnostic workflow efficiency without compromising diagnostic accuracy for csPCa. Keywords: Prostate, MRI, Localization, Oncology, Comparative Studies, Diagnosis Supplemental material is available for this article. ClinicalTrials.gov registration no. NCT05489341 © RSNA, 2026.

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of ZNRF3/RNF43 stimulates cell growth and tumorigenesis through upregulated EGFR signaling. Together, these data suggest ZNRF3 and RNF43 as novel E3 ubiquitin ligases of EGFR and establish the inactivation of ZNRF3/RNF43 as a driver of increased EGFR signaling, ultimately promoting cancer progression. This discovery establishes a connection between two fundamental signaling pathways, EGFR and WNT, at the level of cytoplasmic membrane receptors, uncovering a novel mechanism underlying the frequent co-activation of EGFR and WNT signaling in development and cancer.

Synchronous renal cell carcinoma (RCC) and colorectal cancer are uncommon, and the optimal surgical strategy remains controversial. We report a patient with synchronous RCC and sigmoid colon cancer successfully treated with a one-stage, robot-assisted combined approach using the da Vinci 5 system. A 60-year-old woman presented with severe anemia. Imaging revealed a left-sided renal tumor, sigmoid colon cancer, and a solitary pulmonary metastasis. Both tumors were considered surgical indications, and early intervention was required due to the risk of bowel obstruction. Robot-assisted radical nephrectomy, followed by robot-assisted sigmoid colectomy, was performed in a single session. The total operative time was 4 h 19 min, with minimal blood loss and no intraoperative complications. Simultaneous robotic resection for synchronous RCC and sigmoid colon cancer is feasible and safe in selected patients when supported by careful preoperative planning and multidisciplinary collaboration.

Drugs with multiple anticancer mechanisms have shown promising applications in tumor treatment. Herein, we synthesized a series of ferrocene-pyrazole hybrids (8-11) to assess their anti-pancreatic cancer activities. Among them, compound 11 exhibited higher anti-cancer effects compared to other compounds and showed low toxicity to normal HK-2 cells. The hemolysis experiment shows that compound 11 exhibited low hemolytic activity. Proteomics and metabolomics studies have found that a total of 35 proteins and 58 metabolites (negative mode) showed significantly different abundances in BxPC-3 cells treated with 10 μM compound 11. Subsequent research unveiled that compound 11 eradicates pancreatic cancer cells through the activation of various mechanisms, including ferroptosis and metabolic pathways. These studies may stimulate the development of ferrocene-pyrazole hybrids and provide effective cancer treatment.

To evaluate the prognosis of patients with nonsmall cell lung cancer (NSCLC) who did not undergo surgery after neoadjuvant chemotherapy combined with immunotherapy (NACI). Patients were grouped according to subsequent treatment: radiotherapy (RT) or nonradiotherapy (non-RT), and the prognostic importance of positron emission tomography/computed tomography (PET/CT) was further assessed.

Clear cell renal cell carcinoma (KIRC), the most prevalent pathological renal cell carcinoma (RCC) subtype, makes up approximately 75%-84% of total cases. KIRC is characterized by high heterogeneity, high metastasis rates, and a poor prognosis. Its incidence rate has continued to rise in recent years. We sought to construct new prognostic models to optimize treatment decisions, improve clinical benefits, and explore potential therapeutic targets.

Kidney renal clear cell carcinoma (KIRC) is an aggressive malignancy with limited therapeutic options, highlighting the need for novel biomarkers and therapeutic targets. Although endoplasmic reticulum metallopeptidase 1 (ERMP1) has been implicated in cancer progression, its specific role, clinical significance, and underlying mechanisms in KIRC remain poorly defined.

Cholangiocarcinoma (CCA) is a highly aggressive malignancy. 3-Hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a mitochondrial enzyme involved in ketogenesis, has been linked to tumor progression, but its role in CCA remains unclear. HMGCS2 expression in CCA tissues was analyzed using TCGA data and immunoblotting (IB). Functional assays were performed in CCA cell lines (HuCCT-1 and RBE) and an in vivo xenograft model. Metabolomics explored HMGCS2-mediated metabolic changes. SIRT3-HMGCS2 interactions were examined via molecular docking, IF, CO-IP, GST pull-down, and CHX assays, with mutational analysis identifying interaction sites. IHC assessed clinical samples. HMGCS2 was downregulated in CCA. Overexpression inhibited proliferation and invasion, while knockdown promoted these effects, consistent in vitro and in vivo. Metabolomics showed HMGCS2 enhanced ketone body synthesis, and exogenous ketone bodies mimicked its antitumor effects. SIRT3 deacetylated HMGCS2 at K310 (with plasmid mutation assay), and low HMGCS2/SIRT3 expression correlated with poor patient survival. SIRT3-mediated deacetylation of HMGCS2 promotes ketone body synthesis, suppressing CCA progression. HMGCS2 is a potential therapeutic target for CCA.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Although the hypoxia-inducible factor 1A (HIF1A) pathway is crucial in HCC progression, its regulatory mechanisms remain unclear as mutations in its primary regulator, von Hippel-Lindau tumor suppressor (VHL), are rare in HCC. We aimed to elucidate the role of proliferation and apoptosis adaptor protein 15 (PEA15), identified through proteomic analysis, as a regulator of the VHL/HIF1A pathway and a therapeutic target in HCC. Methods: Proteomic and genomic analyses of over 1,000 HCC samples were conducted, identifying PEA15 amplification. Functional validation involved in vitro and in vivo assays, including gene knockdown, ectopic expression, and antisense oligonucleotide (ASO) therapy in xenograft models. Protein interactions were assessed using immunoprecipitation and ubiquitination assays. Results: We identified 3 clinically distinct HCC subtypes and found that PEA15 was selectively amplified and highly expressed in the mesenchymal (MES) subtype, which exhibited the poorest prognosis. PEA15 acted as a regulator of the VHL/HIF1A pathway and a key oncogene in HCC. The amplification of PEA15 was significantly associated with the poor survival of HCC patients. Moreover, by interacting with the β-domain of VHL, PEA15 promoted HCC cell proliferation and migration by inhibiting VHL's interaction with the VHL/elongin C (ELOC)/elongin B (ELOB)/cullin 2 (CUL2) E3 ligase complex, destabilizing the complex and consequently activating HIF1A. Importantly, pharmacologically inhibiting PEA15 using PEA15 ASO drugs attenuated tumor burden and restored VHL function in a xenograft mouse model. Conclusions: This study identified PEA15 as a potential oncogene in HCC, regulating the VHL/HIF1A axis and driving tumor progression. Targeting PEA15 using ASOs offers a promising therapeutic strategy for HCC, particularly in the MES subtype. These findings provide a basis for further exploration of PEA15-targeted therapies to improve HCC outcomes.

Human leukocyte antigen E (HLA-E) plays a role in tumor immune escape and is associated with poor prognosis in neuroblastoma (NB). This study aimed to investigate the regulatory effect of suberoylanilide hydroxamic acid (SAHA) on HLA-E expression via the PERK/ATF4/CHOP pathway in NB.