Triple-negative breast cancer (TNBC) lacks effective targeted treatments, rendering γδ T cell immunotherapy a promising therapeutic strategy. However, the function of these immune cells is often limited by exhaustion and immunosuppression. This study investigated whether metformin can enhance γδ T cell-mediated immunity against TNBC. Results demonstrated that metformin increased the cytotoxicity, proliferation, and cytokine production of γδ T cells while reducing their exhaustion markers. It differentially modulated cellular metabolism by enhancing oxidative phosphorylation (OXPHOS) and glycolysis in γδ T cells while suppressing these pathways in cancer cells through AMPK-HIF1-α signaling. Metformin also upregulated stress ligands on tumor cells, thereby improving immune recognition. In chemoresistant models, metformin restored γδ T cell function. Clinical data further showed that high AMPK activity and increased γδ T cell infiltration were associated with improved patient survival. These findings indicate that metformin remodels immunometabolism and enhances tumor immunogenicity, supporting its potential as a combinatory agent in γδ T cell-based immunotherapy for TNBC.

Hepatocyte nuclear factor 4 alpha (HNF4α) is a conserved nuclear receptor that governs epithelial identity and metabolic homeostasis across endoderm-derived tissues. In cancer, HNF4α can function as either an oncogene or a tumor suppressor. In colorectal and hepatocellular carcinoma, reduced HNF4α activity accompanies loss of differentiation and tumor progression, consistent with tumor-suppressive functions. In contrast, in pancreatic ductal adenocarcinoma, invasive mucinous adenocarcinoma, and other lineage-defined epithelial tumors, HNF4α can also participate in transcriptional programs that sustain malignant identity, metabolic adaptation, and therapeutic resistance. However, these effects are highly context-dependent and do not imply a uniformly oncogenic role in these tumor types. These divergent functions are shaped by isoform usage, chromatin state, epigenetic regulation, metabolic cues, and transcription factor networks. Rather than acting as a classical oncogene or tumor suppressor in all settings, HNF4α is better understood as a context-dependent regulator of lineage state whose activity may either restrain tumor progression or support tumor maintenance. This mini review highlights the molecular mechanisms that shape HNF4α activity, including isoform biology and epigenetic control, and discusses emerging strategies for selectively inhibiting HNF4α in dependency states or restoring its differentiation-promoting functions in tumors where it is lost.

To evaluate whether 7-T susceptibility-weighted imaging (SWI) can predict glioma's histological grade, Ki-67 labeling index (LI), isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q co-deletion, telomerase reverse transcriptase (TERT) promoter mutation, and O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status of gliomas.

The Muscleblind-like (MBNL) family comprises evolutionarily conserved RNA-binding proteins that interact with target RNAs via zinc finger domains. MBNLs orchestrate RNA processing, particularly alternative splicing, driving the developmental fetal-to-adult isoform switch across numerous target transcripts. This transition is a cornerstone in the process of MBNL-maintained cellular homeostasis and fails in many pathological conditions associated with deregulated expression or function of specific MBNL paralogs. This review provides current insights into the roles of MBNL genes and proteins in both health and disease. We examine their genomic architecture and protein organization and synthesize key insights from animal models to delineate the selective and compensatory functions of individual MBNL paralogs in physiology. To illustrate the roles of MBNLs in disease, we outline nucleotide repeat expansion disorders marked by their functional depletion, with a primary focus on myotonic dystrophy (DM). We also highlight selected cancer studies that have demonstrated the dual roles of MBNLs in tumorigenesis, encompassing both pro-oncogenic and tumor suppressive functions. Finally, using DM as a model, we review evidence for the therapeutic potential of endogenous MBNL gene modulation and argue that analogous strategies could be adapted and tailored to restore MBNL homeostasis in other disorders involving their dysregulation.

Non-small cell lung cancer (NSCLC) is a malignant tumor characterized by high morbidity and mortality, as well as metabolic reprogramming. Enhanced serine synthesis plays a crucial role in the aberrant metabolism of NSCLC. Among the three key enzymes involved in serine synthesis, phosphoserine aminotransferase 1 (PSAT1) requires further investigation to elucidate its regulatory mechanisms in NSCLC.

Thrombocytopenia-absent radius (TAR) syndrome is a rare congenital disorder characterized by bilateral radial aplasia with preserved thumbs and early-onset thrombocytopenia. While hematologic and skeletal abnormalities define the condition, its association with hematologic malignancies is extremely rare, with only a few reported cases of leukemia. Juvenile myelomonocytic leukemia (JMML) is an uncommon pediatric myelodysplastic/myeloproliferative neoplasm frequently linked to RAS pathway mutations. To our knowledge, JMML has not previously been reported in association with TAR syndrome.

The Hippo/YAP signaling pathway is a key regulatory network that governs organ size, tissue homeostasis, cell proliferation, and cell polarity. Aberrant Hippo/YAP signaling contributes to the initiation and progression of multiple cancers, making this pathway an attractive therapeutic target. Although several agents targeting Hippo/YAP have shown promise in preclinical models, clinical translation has been limited. These challenges likely stem from an incomplete understanding of the upstream regulators, downstream effectors, pathway crosstalk, and context-dependent roles of Hippo/YAP across different tumor types. Continued mechanistic investigation is required to clarify these complexities and reveal new therapeutic vulnerabilities. In this review, we summarize the current knowledge of the core components of the Hippo/YAP pathway, its regulatory mechanisms and interactions with other signaling cascades, its dysregulation in cancer, the involvement of microRNAs and lncRNAs in pathway modulation, and emerging therapeutic strategies targeting Hippo/YAP.

Background: From 2019 July 15 to 2022 February 14, the REZOR study enrolled 369 treatment-naïve patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R mutation). Patients were randomly assigned 1:1 to receive either rezivertinib (180 mg/d) plus gefitinib placebo or gefitinib (250 mg/d) plus rezivertinib placebo. Previous results demonstrated significantly improved progression-free survival (PFS) with rezivertinib versus gefitinib and a favorable safety profile. Here, we update the analyses of central nervous system (CNS) outcomes in patients with baseline CNS metastases. Methods: All patients underwent brain magnetic resonance imaging at baseline and each subsequent efficacy evaluation until radiological disease progression or any other treatment discontinuation criteria were met. EGFR mutation status was determined by testing using tissue or plasma samples during screening. Patients with stable, asymptomatic CNS metastasis were eligible for enrollment. The CNS full analysis set (cFAS) comprised patients with baseline CNS metastasis identified on magnetic resonance imaging and evaluated by blinded independent central review according to the Response Assessment in Neuro-Oncology Brain Metastases criteria. Patients with measurable CNS target lesions formed the CNS evaluable-for-response set (cEFR). Results: As of the 2023 November 30 data cutoff, 159 patients had baseline CNS metastasis in the cFAS (rezivertinib: n = 81; gefitinib: n = 78) and 25 in the cEFR (rezivertinib: n = 12; gefitinib: n = 13) per blinded independent central review. In the cFAS, 59 CNS PFS events occurred (rezivertinib: n = 30; gefitinib: n = 29). Median CNS PFS was significantly longer with rezivertinib (24.9 months; 95% confidence interval [CI], 16.5 months-not estimable [NE]) than with gefitinib (15.2 months; 95% CI, 10.5 months-NE), with a hazard ratio of 0.58 (95% CI, 0.34 to 0.99; P = 0.047). In the cEFR, the CNS objective response rate was 83.3% (95% CI, 51.6% to 97.9%) with rezivertinib and 76.9% (95% CI, 46.2% to 95.0%) with gefitinib (odds ratio = 1.50; 95% CI, 0.20 to 11.0; P = 0.690). No new safety findings were observed. Conclusions: Rezivertinib demonstrated a statistically significant superior CNS efficacy over gefitinib as first-line treatment in advanced EGFR-mutated non-small cell lung cancer patients with baseline CNS metastases. The safety profile was consistent with previous analyses. Trial registration: NCT03866499 (ClinicalTrials.gov).

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid malignancies, characterized by aggressive biology and a paucity of effective treatments. Activating mutations in KRAS occur in more than 90% of cases and are fundamental to tumor initiation, progression, therapeutic resistance, and immune exclusion, establishing KRAS as the dominant oncogenic driver in PDAC. Long considered undruggable, KRAS has recently become a viable therapeutic target with the development of allele-specific inhibitors as well as pan-RAS(ON) agents capable of broadly suppressing mutant RAS signaling. Preclinical models and early-phase clinical trials demonstrate meaningful antitumor activity, with emerging evidence of tumor microenvironment remodeling and delayed resistance. Combination strategies integrating KRAS-directed therapies with chemotherapy, vertical pathway inhibition, immunotherapy, and emerging approaches such as KRAS degradation and RNA-targeted approaches are being explored to improve the depth and durability of response. Together, these advances signal a paradigm shift toward molecularly guided treatment strategies in PDAC and offer a promising path forward in a disease with substantial unmet clinical need.

Natural ferritin Fn) is a cage-like protein with a central cavity, making it a promising vehicle for drug delivery. However, its non-specific accumulation in iron-metabolizing organs impairs targeting precision and therapeutic efficacy. To overcome this challenge, we aimed to develop a novel biomimetic nanoplatform based on manganese-mineralized ferritin loaded with dihydroartemisinin (DHA@MFn) for precise ovarian cancer treatment, enabling controlled drug release and amplified therapeutic effects within the tumor microenvironment.

Cantharidin (CTD) is a natural anticancer compound whose clinical application is limited by poor water solubility, low bioavailability, and significant toxicity. To develop a more effective and safer therapeutic strategy, we proposed a synergistic combination therapy by integrating CTD with staurosporine (STS), a protein kinase inhibitor that shares complementary mechanisms of action targeting the mTOR/HIF-1α/VEGF pathway. We further developed an aptamer-guided liposomal nanosystem for the co-delivery of CTD and STS (Apt/CTD-STS/NL), aiming to enhance tumor targeting, improve bioavailability, and reduce the systemic toxicity of both drugs.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease that typically requires multimodal treatment. Recently, immunotherapy strategies targeting the tumor microenvironment (TME) have reshaped the therapeutic approach for MIBC. Our study explores the expression of immune checkpoint biomarkers TIGIT, LAG-3, and PD-L1 across molecular subtypes of MIBC.

'Cutaneous T-cell lymphoma (CTCL), particularly tumor stage mycosis fungoides (MF), presents significant therapeutic challenges due to limited treatment efficacy. This study addresses the unmet need for novel targeted therapies targeting the constitutively hyperactive STAT3/5 pathway.

Diffuse Midline Glioma (DMG), often formerly called Diffuse Intrinsic Pontine Glioma (DIPG) when in the brainstem, DMG/DIPG is a lethal pediatric brain tumor defined by infiltrative growth, resistance to conventional therapies, and a profound immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs), including resident microglia and infiltrating monocyte-derived macrophages, are the predominant immune population in DMG/DIPG. These cells adopt an immunosuppressive, pro-tumor state, promoting immune evasion and limiting the efficacy of therapies such as chimeric antigen receptor (CAR) T cells. Reprogramming TAMs toward a pro-inflammatory, anti-tumor phenotype offers a promising strategy to remodel the DMG/DIPG microenvironment. This review is the first to provide a comprehensive, integrative perspective on TAM-directed strategies in DMG/DIPG, spanning molecular, epigenetic, and biophysical approaches. We summarize TAM-mediated tumor progression and therapy resistance, and discuss molecular reprogramming strategies, including colony-stimulating factor 1 receptor (CSF1R) inhibition, microRNA-based circuits, and epigenetic modulators such as histone deacetylase (HDAC) and bromodomain and extra-terminal domain (BET) inhibitors. Nanoparticle-mediated delivery systems allow selective TAM targeting and enhanced blood-brain barrier (BBB) penetration. Additional strategies, including oncolytic viruses and macrophage-specific checkpoint blockade (e.g., CD47/SIRPα axis inhibitors), simultaneously promote tumor clearance and immune activation. We also highlight emerging biophysical approaches to modulate TAM function in situ. Photodynamic therapy (PDT) induces immunogenic cell death and pro-inflammatory macrophage activity, while focused ultrasound (FUS) transiently disrupts the BBB to enhance drug delivery and immune infiltration. Photobiomodulation and low-level light therapy (LLLT) may influence macrophage metabolism and phenotype, though their application in DMG/DIPG remains largely unexplored. Finally, we discuss combinatorial strategies integrating TAM reprogramming with CAR T cell therapy or chemotherapy to overcome the immunologically "cold" nature of DMG/DIPG. By uniting mechanistic insights with translational opportunities, this review establishes TAM reprogramming as a critical, underexplored frontier in DMG/DIPG immunotherapy, offering the potential to render an otherwise intractable tumor immunologically targetable.

Hsa-miR-99a has been linked to the advancement of several malignancies, including colorectal cancer (CRC). This investigation seeks to elucidate its function and regulatory network in CRC.

Undifferentiated small round cell sarcoma (USRCS) are a rare, aggressive group of tumors associated with rapid progression, metastasis, and poor prognosis. Preoperative diagnosis remains elusive, particularly for extraosseous variants, and effective treatments are lacking. This case reports the use of pembrolizumab, bevacizumab, and conventional chemotherapy (gemcitabine plus paclitaxel) as a first-line treatment for a patient with primary USRCS in the gallbladder neck; the patient achieved remarkable partial remission for more than 9 months. This case represents the second documented instance of gallbladder USRCS and the first managed with this specific combination regimen. These findings suggest that integrating immunotherapy and targeted agents with conventional chemotherapy may offer a promising therapeutic strategy for USRCS.

This study aimed to evaluate the diagnostic yield and complications associated with computed tomography (CT)-guided transthoracic core-needle biopsy (CNB) of lung lesions and to identify factors influencing biopsy outcomes.

Gastric carcinoma poses a significant global health challenge, often diagnosed late due to its similarity to chronic gastric conditions. Helicobacter pylori (Hp) infection plays a crucial role in gastric carcinogenesis through inflammation and the release of virulent products.

Ovarian cancer remains the most lethal gynecologic cancer and has the worst prognosis among all female reproductive malignancies worldwide. In Ethiopia, ovarian cancer is the third most prevalent malignancy among women, following breast and cervical cancers. Despite extensive research on the topic, evidence regarding the determinants of mortality among ovarian cancer patients remains limited. Therefore, the primary aim of this study was to identify predictors of ovarian cancer mortality among patients receiving care at oncology centers in Addis Ababa, Ethiopia.

Pulmonary metastasectomy is an established part of the multimodal treatment of various malignant diseases. While the procedure typically focuses on complete removal of metastatic lesions, the role of mediastinal lymph node involvement remains unclear. We aimed to analyze the prevalence of lymph node involvement and its impact on prognosis in patients undergoing pulmonary metastasectomy.