Search Results (4,305)

Myeloid cell leukemia-1 (MCL-1) is a cellular survival protein belonging to the Bcl-2 protein family and is overexpressed in human colorectal cancer (CRC). Background: This study aimed to reduce cancer progression by suppressing the MCL-1 protein using PROTAC MCL-1 Degrader-1 and Trametinib, with the aim of overcoming the apoptosis resistance caused by high MCL-1 expression levels in colorectal cancer cells. Methods: Therefore, we tested the cell viability, proliferation, mitochondrial membrane potential, cell cycle progression, and cell death potential of MCL1-specific PROTAC Mcl-1 Degrader-1 and the combination of PROTAC Mcl-1 Degrader-1 and Trametinib in colorectal cancer cell lines using different methods such as WST-8 assays, real-time cell analysis, MMP/JC-1 staining assays, flow cytometry, and Western blot analysis. Results: The results suggest that PROTAC Mcl-1 Degrader-1 is associated with dose- and time-dependent reductions in cell proliferation in colorectal cancer cells. Under the experimental conditions used in this study, PROTAC MCL-1 Degrader-1 showed limited effects on the migratory potential of colorectal cancer cells but was associated with changes in cell cycle distribution, including an increased proportion of HT-29 cells in the G2/M phase. In addition, combination treatment with PROTAC MCL-1 Degrader-1 and trametinib was associated with greater reductions in cell viability and proliferation than either monotherapy. The combination treatment was also accompanied by changes in mitochondrial membrane potential and increased apoptotic cell populations, with a higher proportion of early apoptotic cells observed in HT-29 and COLO-205 colorectal cancer cell lines. Conclusion: Our findings suggest that the reduction in MCL-1 protein levels observed following PROTAC Mcl-1 Degrader-1 treatment may contribute to its potential therapeutic relevance in colorectal cancer. Full article

Neuroblastoma is an aggressive pediatric malignancy with limited therapeutic options for high-risk disease, underscoring the need for alternative treatment strategies. Drug repurposing offers a promising approach to accelerate the identification of effective anti-cancer agents. In this study, we investigated the anti-carcinogenic effects of hydroquinidine, a class IA antiarrhythmic ion channel blocker, and spiramide, a dopamine D₂/serotonin 5-HT₂ receptor antagonist and endoplasmic reticulum stress inducer, in SH-SY5Y human neuroblastoma cells. Cells were treated with increasing concentrations of each compound and evaluated using cell viability, colony formation, wound healing, proliferation, apoptosis, and quantitative gene expression assays. Both compounds induced a dose-dependent reduction in cell viability, with spiramide exhibiting greater potency than hydroquinidine. Functional assays revealed significant suppression of clonogenic survival, cell migration, and DNA synthesis, accompanied by increased oxidative stress and cell death. Molecular analyses demonstrated coordinated transcriptional regulation of apoptosis- and cell cycle-related genes, characterized by upregulation of BAX, CDKN1A, and CDKN1B, and downregulation of BCL-2 and CCND1. Notably, spiramide consistently produced stronger cytotoxic and wound-closure inhibitory effects, suggesting a greater contribution of oxidative stress- and apoptosis-associated pathways. Collectively, these findings indicate that hydroquinidine and spiramide disrupt neuroblastoma cell growth through complementary stress- and cell cycle-associated pathways and identify them as promising candidates for further preclinical evaluation. Full article

Background: Next-generation sequencing (NGS) and the initiation of biomarker-driven first-line (1L) treatment on overall survival (OS) was evaluated in advanced/metastatic non-small-cell lung cancer (a/mNSCLC). By applying a time-dependent regression modeling approach accounting for fluidity of clinical care, this study aimed to capture the dynamic interplay between NGS testing, turnaround time (TaT), treatment decisions and timing of initiation, and outcomes more comprehensively than traditional static analyses. Methods: This study was a retrospective observational study using the US Flatiron Health EHR-derived de-identified database. Eligible adults had non-squamous a/mNSCLC and received blood-based (B-NGS) or tissue-based (T-NGS) NGS within 90 days of diagnosis (1 January 2018–30 June 2023). A time-dependent covariate captured the NGS TaT, presence of a targetable alteration, time to 1L initiation, and 1L regimen (targeted concordant vs. discordant). OS was measured from the NGS order date to death. Results: A total of 1806 patients underwent B-NGS and 2583 underwent T-NGS. Starting empiric discordant 1L therapy before NGS results was associated with higher mortality versus initiating targeted concordant therapy after biomarker identification: B-NGS hazard ratio (HR): 1.58 (95% CI, 1.10–2.26); T-NGS HR: 1.07 (0.82–1.39). Considering discordant 1L therapy irrespective of timing, mortality remained higher versus targeted concordant therapy: B-NGS HR: 1.35 (1.04–1.74); T-NGS HR: 1.24 (0.98–1.56). Conclusions: This study demonstrates that waiting for comprehensive molecular profiling results before starting 1L treatment enables the delivery of appropriate biomarker-driven therapy, which translates into improved patient outcomes. Delays in NGS result availability or treatment initiation were linked to worse survival, underscoring the need for streamlined diagnostic workflows and rapid testing modalities. Full article

Primary liver malignancies, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although systemic therapies have advanced substantially, intrahepatic tumor progression, liver failure, and portal hypertension continue to drive adverse outcomes in many patients. Interventional radiology plays a central and expanding role in the multidisciplinary management of these tumors by providing image-guided locoregional therapies for local tumor control, downstaging, bridging transplantation or resection, palliation, and potential survival benefit. This narrative review summarizes current evidence and technical considerations for major locoregional approaches, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization, transarterial radioembolization, endobiliary therapies, stereotactic body radiation therapy, irreversible electroporation, histotripsy, high-intensity focused ultrasound, hepatic arterial infusion, and brachytherapy. Interventional radiology also contributes to preoperative liver optimization through portal vein embolization, liver venous deprivation, lobar radioembolization to induce contralateral hypertrophy, and, in some patients, portal decompression before hepatic resection. For hepatocellular carcinoma, ablation and transarterial therapies are integrated into stage-based treatment algorithms and may provide curative-intent treatment in some patients. In intrahepatic cholangiocarcinoma, locoregional therapies provide meaningful disease control and may prolong survival, particularly when combined with systemic therapy. In combined hepatocellular cholangiocarcinoma, treatment remains individualized because of limited prospective data and heterogeneous tumor biology. Beyond cytoreduction, locoregional therapies can modulate the tumor immune microenvironment through immunogenic cell death, antigen release, cytokine signaling, and vascular remodeling, providing a rationale for combination strategies with immune checkpoint inhibitors, anti-angiogenic agents, and targeted therapies. As treatment paradigms evolve, the future of interventional radiology in primary liver cancer will depend on appropriate patient selection, optimized dosimetry and technique, integration with molecular and immunologic biomarkers, and coordinated multidisciplinary care. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma and one of the most common hematological neoplasia. Entropy is a statistical measure of randomness that characterizes the texture of an input image and measures tissue complexity. Methods: Image processing and computer vision analysis were performed on a series of 114 diagnostic DLBCL cases and 44 reactive lymphoid tissues stained with hematoxylin and eosin (H&E). Histological entropy was measured to differentiate between reactive lymphoid tissue and DLBCL and predict clinical evolution. At protein level, immunohistochemistry analyzed Ki67, LMO2, MYC, MDM2, CDK6, E2F1, BCL2, CASP8, MYOB, TP53, cPARP, cCASP3, ISY1, TNFAIP8, CSF1R, CD163, PD-L1 and IL-10 markers. Gene expression analysis using the NanoString nCounter PanCancer Immune Profiling Panel was performed in 29 cases. Results: In comparison with reactive lymphoid tissue, DLBCL was characterized by lower entropy (7.32 ± 0.16 vs. 6.82 ± 0.44, respectively; p < 0.001). Within the DLBCL diagnostic category, higher entropy was associated with poor overall survival and death events within the first 2 years (hazard-risk = 2.4, p = 0.004) and lower entropy with a moderate and more favorable outcome (hazard-risk = 0.4, p = 0.004). High entropy was also correlated with ECOG performance status ≥ 2, lower protein expression of apoptosis markers of cPARP and cCASP3, and upregulation of specific immuno-oncology genes such as STAT3, BTK, CASP8, CD47, VCAM1, and MYD88. The prognostic value of entropy was independent of the international prognostic index (IPI), Epstein–Barr virus (EBER), and cell of origin (Hans). Conclusions: The histological evaluation of entropy is useful for the differential diagnosis of reactive lymphoid tissue and DLBCL and is a predictive factor of DLBCL prognosis. Full article

Background: Generating personalized anti-tumor immune responses remains a primary objective of precision oncology, yet conventional autologous platforms face critical biological and logistical constraints. While current research modifies allogeneic lines to evade host clearance, this perspective outlines a translational framework designed to leverage host-donor incompatibility as an active immunomodulatory asset to remodel the solid tumor microenvironment (TME). The framework proposes expanding a systemic pool of circulating, allo-specific host type 1 helper (Th1) memory cells via iterative intradermal injections of completely mismatched, activated donor Th1 cells, followed by a systemic intravenous rechallenge to provoke a controlled host-versus-graft (HvG) rejection response. Rapid intravascular clearance of donor cells is hypothesized to drive a transient, Type 1 cytokine wave that activates host effector populations via bystander pathways, promoting their extravasation into the tumor stroma to induce immunogenic cell death (ICD). This paradigm is contextualized by Phase 2B data in refractory microsatellite stable (MSS) metastatic colorectal cancer, where a dual-route allogeneic Th1 regimen demonstrated a median overall survival (OS) signal of 16.4 months despite an 89.5% conventional radiological progression rate. Ultimately, this framework provides a predictable, non-engineered conceptual mechanism to elicit a patient-specific adaptive immune response without ex vivo customization. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC), the predominant malignant subtype of kidney cancer, is the leading cause of death among renal cell carcinoma patients. Although a subset of ccRCC patients benefit from select immune checkpoint inhibitors (ICIs), prognosis remains poor. While PD-1 and PD-L1 have been extensively studied, the prevalence and distribution of other immune checkpoints (ICs) and their relationship with epithelial-to-mesenchymal transition (EMT) remain poorly characterised. Here, we investigated the interplay between twenty ICs and EMT markers and assessed their combined prognostic relevance in ccRCC patients. Methods: Transcriptomic profiling and integrated bioinformatic analyses were performed, including differential expression, correlation analyses, survival analyses, forest plot analyses, ROC curve evaluation, and OncoPrint visualisation, complemented by analysis of single-cell RNA sequencing data, immunohistochemistry, and multiplex secretory IC (LegendPlex) assays. Results: Transcriptomic profiling of over 500 ccRCC tumours versus normal kidney tissue revealed dysregulation of ICs, particularly LAG3 and NT5E. Notably, expression of ICs, including LAG3 and NT5E, was associated with poor overall survival in 415 ccRCC patients. ICs that synergised with the EMT phenotype provided improved prognostic discrimination compared to individual ICs. Correlation analyses, single-cell RNA sequencing, and immunohistochemistry demonstrated an association between EMT-associated tumours and expression of LAG3 and NT5E. ROC analysis indicated modest prognostic performance of LAG3 and NT5E. Conclusions: Collectively, this study identifies an EMT–IC axis in ccRCC and demonstrates its relevance to tumour biology and patient outcomes, highlighting LAG3 and NT5E as potential prognostic markers and therapeutic targets that warrant further investigation. Full article

Background/Objectives: Cancer metastasis is responsible for most cancer-related deaths, yet the precise anatomical and physiological routes by which cancer cells disseminate remain incompletely defined. This review aims to present an integrated model of lymphatic and hematogenous dissemination that provides a unified framework for understanding metastatic progression. Methods: The published literature on lymphatic biology, microvascular physiology, tumor immunology, and cancer metastasis was critically reviewed and integrated to develop a comprehensive anatomical and physiological model of cancer dissemination. Results: The proposed model identifies lymphatic dissemination as the predominant metastatic route in many solid tumors. Cancer cells enter structurally permissive initial lymphatic capillaries and are transported to the sentinel lymph node (SLN), where interactions with the tumor microenvironment may eliminate disseminated cells, maintain dormancy, or facilitate immune escape and further dissemination. Cancer cells that survive within or escape beyond the SLN subsequently travel through collecting lymphatics and the thoracic or right lymphatic duct to enter the systemic venous circulation. Following cardiopulmonary transit, surviving cells may be redistributed through the systemic arterial circulation to distant organs. A secondary pathway involves direct hematogenous intravasation through post-capillary venules, where reduced shear stress, increased endothelial permeability, and permissive endothelial biology facilitate entry into the venous circulation. Thus, lymphatic and direct venular pathways ultimately converge in the venous circulation before systemic arterial dissemination. Conclusions: This unified model integrates lymphatic and hematogenous dissemination into a coherent anatomical and physiological framework. By emphasizing the SLN as an early immunologic checkpoint and the arterial circulation as the final distribution network for disseminated cancer cells, this review provides a conceptual basis for understanding metastatic patterns and identifying biomarkers and therapeutic vulnerabilities. Full article

Acute myeloid leukaemia (AML) exhibits profound metabolic plasticity that enables leukaemic cells to survive environmental stress, nutrient limitation, and therapeutic pressure, ultimately driving disease persistence and relapse. While genetic and epigenetic alterations have guided risk stratification and therapeutic development, accumulating evidence indicates that nutrient-dependent metabolic rewiring represents a critical and targetable vulnerability in AML. Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor whose intracellular availability is tightly linked to dietary intake of its precursors, including tryptophan, niacin (vitamin B3), nicotinamide, and nicotinamide riboside. NAD supports redox balance, mitochondrial metabolism, DNA repair, and stress adaptation, processes that are particularly critical for leukaemic stem cell survival under therapeutic stress. Recent studies demonstrate that AML cells, including those resistant to venetoclax- and hypomethylating agent–based regimens, exhibit heightened dependence on the NAD salvage pathway mediated by nicotinamide phosphoribosyltransferase (NAMPT). Pharmacological inhibition of this pathway induces profound NAD depletion, mitochondrial dysfunction, and selective leukaemic cell death. In this review, we integrate nutritional biology with emerging translational evidence to examine NAD metabolism as a nutrient-regulated metabolic vulnerability in AML. We discuss dietary sources and systemic regulation of NAD, the role of NAD-dependent pathways in leukaemic persistence, the translational exploitation of NAD salvage dependency, and the emerging controversy surrounding NAD supplementation in cancer. Finally, we highlight key knowledge gaps and future directions at the interface of nutrition, metabolism, and therapy response in AML. Full article

Background/Objectives: Published data on reliable prognostic biomarkers for pulmonary pleomorphic carcinoma (PPC), a rare, aggressive subtype of non-small cell lung cancer, are limited. Programmed death-ligand 1 (PD-L1) has been studied; however, the prognostic impact of other immunoregulatory molecules, such as CD73, CD155, and Ki-67 and their combined expression profiles, remains unclear. Methods: We retrospectively analyzed data of 47 patients who had undergone macroscopic complete resection of PPC between January 2000 and December 2022. Immunohistochemistry for PD-L1, CD73, CD155, and Ki-67 was performed. Cut-off values were determined by receiver operating characteristic analysis for cancer-specific death. The primary endpoint was the association between each biomarker and overall survival (OS) or cancer-specific survival (CSS). The secondary endpoint was the prognostic value of combined biomarker profiles, particularly PD-L1 with CD73, CD155, or Ki-67. Results: At a positivity threshold of 1%, the positivity rates were 70.2% for PD-L1, 89.4% for CD73, 91.5% for CD155, and 83.0% for Ki-67. There were no statistically significant differences in OS or CSS between groups with high expression and those with low expression for any single marker. Secondary endpoint analysis showed that low PD-L1 and low CD73 predicted significantly poorer OS (p = 0.046) and low PD-L1 and low Ki-67 predicted significantly poorer CSS (p = 0.039) compared with other combinations. Conclusions: Primary endpoint analyses showed no statistically significant association between any single marker and prognosis in PPC. In contrast, secondary endpoint findings indicated that concurrent low PD-L1 with either low CD73 or low Ki-67 identified subsets with significantly poorer outcomes. The present findings provide a basis for further investigation of biomarker combinations for prognostic assessment in this rare lung cancer. Because of the limited sample size, these findings are exploratory and require validation in larger independent cohorts. Full article

Experimental evidence has shown that gallic acid (GA), a naturally occurring polyphenolic compound, and docetaxel (DTX), a taxane chemotherapeutic agent, each possess antitumor activity against multiple cancer types. Although both compounds have been investigated individually, their combined effects in triple-negative breast cancer (TNBC) have received limited attention, and the molecular basis of their interaction remains unclear. The present study examined the in vitro effects of GA and DTX in MDA-MB-231 TNBC cells while simultaneously assessing their comparative cytotoxicity in HaCaT human keratinocytes. Evaluation of treatment efficacy included measurement of cell viability by the MTT assay and assessment of drug interactions using the Chou–Talalay combination index (CI) method. Apoptosis together with cell-cycle distribution was subsequently examined using both Annexin V/PI flow cytometry and TALI^® image-based cytometry. Additional analyses included β-tubulin immunofluorescence (IF), caspase-9 immunocytochemistry, ELISA, wound-healing assays, quantitative real-time PCR, and bioinformatic analyses to investigate treatment-associated biological alterations. Combined exposure to GA and DTX produced a significant reduction in cell viability and exhibited synergistic activity in MDA-MB-231 cells. The coordinated biological response to the combined treatment was characterized by increased apoptotic cell death, arrest of the cell cycle at the G2/M phase, extensive disorganization of the β-tubulin network, and enhanced caspase-9 immunoreactivity. Beyond its effects on cell survival, the combined regimen substantially decreased the release of IL-6, IL-8, and TNF-α, limited wound-healing capacity, and reshaped the expression profile of the apoptosis- and cell cycle-related genes BCL2, BAX, CASP9, and CDKN1A. Bioinformatic analyses further revealed enrichment of apoptosis- and cell-cycle-associated pathways that were generally consistent with the experimental observations. The overall pattern of experimental responses indicates that combining GA with DTX enhances the in vitro antitumor efficacy of DTX in TNBC cells by simultaneously influencing apoptotic pathways, cell-cycle regulation, inflammatory cytokine secretion, and cellular migratory capacity. Although the bioinformatic findings provide supportive hypothesis-generating evidence, additional studies using three-dimensional models, in vivo experiments, and functional validation approaches are necessary to confirm the underlying molecular mechanisms and to further define the translational potential of this therapeutic combination. Full article

Objective: Squamous cell carcinoma antigen (SCC-A) is a widely used biomarker for squamous cell cervical carcinoma and pretreatment elevation is associated with poor prognosis. Normalization during chemoradiation correlates with PET-CT response and survival. This study assessed the prognostic value of SCC-A normalization for biopsy-proven pathological response and survival outcomes. Materials and Methods: This retrospective single-center cohort study included patients with locally advanced or node-positive squamous cell cervical cancer treated with definitive chemoradiation at the Medical University Innsbruck between 2008 and 2023. Eligible patients had baseline SCC-A ≥ 2 ng/mL and at least two additional measurements within 42 days of treatment. SCC-A normalization was evaluated at predefined weekly time points. Associations with biopsy-assessed residual disease, PFS, and OS were assessed. Results: Of 186 screened patients, 83 met the inclusion criteria. Within 42 days, 70% achieved SCC-A normalization, with a median time of 21 days (IQR 19–32). Among predefined time points, normalization by day 28 was associated with reduced odds of residual disease (OR 0.14; 95% CI 0.04–0.44) and improved PFS (HR 0.28; 95% CI 0.12–0.63) and OS (HR 0.37; 95% CI 0.14–0.96), remaining independently significant after multivariate adjustments. Conclusions: SCC-A normalization during chemoradiation is a non-invasive independent biomarker of treatment response. Normalization within 28 days identifies patients at low risk of residual disease, progression, and death, supporting its use for early risk stratification and response monitoring for potential treatment adaptations. Full article

Epstein–Barr virus (EBV) is a highly prevalent oncogenic virus that establishes persistent infection in most of the human population and is strongly associated with several lymphoid and epithelial malignancies, particularly nasopharyngeal carcinoma, gastric carcinoma, and lymphoepithelial carcinoma. This review summarizes current knowledge on the relationship between EBV infection and apoptosis regulation in epithelial cancers, with emphasis on how viral persistence may contribute to tumor cell survival and therapeutic resistance. The manuscript reviews evidence on EBV genome organization, latent and lytic infection programs, the epidemiology of EBV-associated epithelial tumors, and the main intrinsic and extrinsic apoptotic pathways. It then discusses how viral proteins, including latent membrane proteins, Epstein–Barr nuclear antigen 1 (EBNA1), BHRF1, and BARF1, as well as EBV-encoded microRNAs, modulate key apoptotic regulators such as p53, Bcl-2 family members, death receptor pathways, and caspases. Current evidence indicates that EBV can promote apoptosis resistance through coordinated effects on mitochondrial and death receptor-mediated cell death. Understanding these mechanisms may help clarify the contribution of EBV to epithelial oncogenesis and support therapeutic strategies aimed at restoring apoptotic sensitivity in EBV-associated tumors. Full article

Vitiligo is a multifactorial depigmentation disorder involving complex interactions among oxidative stress, immune dysregulation, inflammatory signaling, and programmed cell death pathways, which act as a central driver of melanocyte dysfunction and loss, interacting with immune-mediated cytotoxicity and intrinsic cellular susceptibility. Excessive reactive oxygen species (ROS) disrupt mitochondrial integrity, impair redox homeostasis, suppress microphthalmia-associated transcription factor (MITF)-dependent melanogenesis, and induce melanocyte apoptosis. Concomitant dysfunction of the nuclear factor erythroid 2-related factor 2 (NRF2)/antioxidant response element (ARE) axis further exacerbates oxidative injury by limiting endogenous antioxidant capacity. Current therapeutic approaches, including corticosteroids, phototherapy, and targeted immunomodulators, achieve partial repigmentation but do not adequately resolve melanocyte-intrinsic redox imbalance. This structured narrative review comprehensively integrates mechanistic and translational evidence to define phytocompounds as redox-active, multi-target modulators in vitiligo. Plant-derived polyphenols, flavonoids, terpenoids, and related metabolites are shown to attenuate ROS accumulation, preserve mitochondrial function, activate NRF2-dependent antioxidant signaling, and restore MITF-mediated expression of tyrosinase and associated melanogenic enzymes. Furthermore, coordinated modulation of MAPK, PI3K/Akt, and JAK/STAT pathways highlights their capacity to regulate immune–oxidative crosstalk and promote melanocyte survival. Despite promising preclinical and emerging clinical evidence of repigmentation efficacy, translational progress remains limited by poor phytochemical standardization, insufficient transcriptional and proteomic validation, suboptimal stability and dermal bioavailability, and a lack of rigorously designed clinical trials. Collectively, this review provides a mechanistic framework linking redox dysregulation to melanocyte failure and positions phytocompounds as rational candidates for adjunctive or stand-alone antioxidant-based therapies, while defining critical priorities for clinical translation. Full article

Tumor-associated macrophages (TAMs) represent a predominant immune cell population within the tumor microenvironment (TME). To adapt to the metabolically hostile conditions of the TME, characterized by nutrient deprivation and accumulation of metabolic waste products, TAMs undergo metabolic reprogramming to evade cell death. These adaptations enable TAMs to utilize alternative metabolites as energy sources and mitigate metabolic stress through enhanced cystine uptake and activation of hypoxia-inducible factor pathways, thereby supporting their survival and function. However, the key molecular regulators that prevent TAMs death in response to dynamic metabolic changes during tumor progression remain poorly understood. Through integrated multi-omics analyses and experimental validation, we observed that increased AMPK activation during tumor progression is associated with transcriptomic and proteomic features indicative of reduced susceptibility of TAMs to multiple forms of cell death. Conditional deletion of AMPK in TAMs reprogrammed the expression of cell death-related genes and was associated with increased apoptosis, ferroptosis, and notably, disulfidptosis. Clinical correlation analyses revealed that AMPK activity in TAMs was inversely associated with the expression of disulfidptosis-, ferroptosis-, and apoptosis-related gene signatures. Furthermore, tumors characterized by concurrent enrichment of AMPK signaling and TAMs infiltration exhibited lower disulfidptosis, ferroptosis, and apoptosis signature scores, which were associated with a more malignant phenotype. Collectively, our findings suggest that AMPK activity is associated with TAM survival and tumor progression and with reduced susceptibility to multiple forms of cell death, including disulfidptosis. These findings provide evidence linking AMPK activity to metabolic adaptation and cell death resistance in TAMs and suggest its potential as a therapeutic target for cancer intervention. Full article