Search Results (21,953)

Lung cancer recurrence and therapeutic resistance are driven by cancer stem cells (CSCs), yet clinically available CSC-targeted therapies remain lacking. To identify actionable anti-CSC agents, we screened 1018 FDA-approved drugs using a 3D sphere culture system enriching lung CSC-like cells. Trimebutine, a gastrointestinal motility regulator targeting G-protein-coupled receptors (GPCRs), was identified as a potent agent with over 49.5-fold higher selectivity toward lung CSC-like cells (SI > 49.55) compared with standard therapies such as cisplatin (SI = 1.39) and gefitinib (SI = 1.00). In H460-SP spheres, trimebutine markedly impaired sphere-forming capacity, reduced cell viability, and downregulated key CSC surface markers (CD133, CD44) alongside stemness regulators (c-MYC, EpCAM, BMI1, OCT3/4, NANOG, SOX2, SMAD3). Mechanistically, trimebutine suppressed overexpressed calcium and potassium channels (CACNA1F, CACNA1B, CACNA1E, CACNA1H, KCNH2), attenuating downstream YAP/TAZ–TEAD signaling within the Hippo pathway to trigger apoptosis. In combination with cisplatin, trimebutine exhibited strong synergistic efficacy (Chou–Talalay combination index, CI = 0.015–0.228) in H460-SP spheres and patient-derived lung tumor organoids, suppressing cell viability, stemness marker suppression, and apoptotic cleavage of caspase-3 and PARP compared to monotherapies. Overall, trimebutine targets lung CSC populations by disrupting GPCR–ion channel–Hippo signaling crosstalk, providing a strong preclinical rationale for trimebutine–cisplatin combination strategies to overcome drug resistance and recurrence in lung cancer. Full article

Breast cancer remains the most prevalent malignancy among middle-aged and elderly women with underlying health conditions, with triple-negative breast cancer (TNBC) representing a notably aggressive subtype associated with poorer clinical outcomes. Prunus africana (P. africana) has been reported to contain bioactive compounds with notable antioxidant and anticancer properties. Bark extracts obtained using water, as well as single (100%) and binary (50% v/v) solvents of methanol and ethanol (MeOH-100, EtOH-100, MeOH-50, and EtOH-50), were evaluated for their antioxidant activity, apoptosis-inducing effects, and modulation of signaling pathways in selected breast cancer cell lines. Antioxidant activity was measured via FRAP, DPPH radical scavenging, and TEAC assays; cytotoxic activity and pathway modulation were assessed using MTS, human apoptosis, and phospho-RTK array assays. While the EtOH-100 extract presented the lowest extraction yield of 3.22%, it showed the highest total phenolic (505.96 mg GAE/g) and total flavonoid (2.53 mg RU/g) contents and antioxidant activities (2.25 mM Fe²⁺/g and 311.68 mM TE/g), and the lowest EC₅₀ (0.21 mg/mL), comparable to ascorbic acid (0.18 mg/mL). EtOH-100 also notably induced apoptosis in HCC1806 as shown by increased cleaved caspase-3, HSP60, and HSP27 expression, and sustained catalase levels. Phospho-RTK array analysis revealed early silencing of HGF and transient upregulation of EGF and Insulin R following EtOH-100 extract treatment, suggesting modulation of oncogenic signaling. These findings highlight the therapeutic potential of P. africana, particularly the EtOH-100 extract, as a viable treatment for TNBC. Full article

Background: Adipose-derived stem cells (ADSCs) are readily harvestable, tumour-homing cells that have been engineered as vehicles for antitumour agents. TNF-related apoptosis-inducing ligand (TRAIL) selectively triggers apoptosis in many cancer cells through death receptors DR4/DR5, while sparing most healthy cells. To date, only human TRAIL has been studied in such delivery systems; a fully homologous rat model (rat TRAIL delivered by rat ADSC) has not been tested, despite being essential for future syngeneic in vivo studies. Methods: In this pilot, exploratory study, we lentivirally transduced rat ADSC (rADSC) to express myc-tagged rat TRAIL, characterized the expression of TRAIL-pathway components in rADSC and three rat mammary carcinoma cell lines (RBA, HH-16.cl.4, SHZ-88) at the mRNA and protein levels, and assessed the antitumour effect of rTRAIL-rADSC using recombinant TRAIL dose–response, supernatant transfer, direct co-culture, and nine-day insert co-culture assays. Results: rADSCs were successfully transduced and produced cell-associated rat TRAIL (66.2 pg per 50,000 cells versus 4.4–5.7 pg in controls; p < 0.05); this ELISA measures total cell-associated (intracellular plus membrane-anchored) TRAIL rather than soluble TRAIL. rADSC expressed markedly higher levels of the decoy molecule osteoprotegerin and of DR4/DR5 than the cancer cells. Two of three cancer lines (RBA, HH-16.cl.4) were susceptible to rat TRAIL, and rTRAIL-rADSC reduced their growth and increased the proportion of dead cells, with morphological features compatible with both apoptosis and necrosis, most markedly in HH-16.cl.4; the effect was separable from the empty-vector control in HH-16.cl.4 but not in RBA. Conclusions: In this pilot study, homologous rat TRAIL delivered by rADSC is feasible and increases cell death in TRAIL-susceptible rat mammary cancer cells, but the effect is moderate at most, contact-dependent, and in one of two susceptible lines not attributable to TRAIL itself. These findings define both the potential and the limitations of a fully translational rat model of TRAIL-based biologic brachytherapy and provide a foundation for future in vivo studies. Full article

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer, but resistance and recurrence remain major clinical challenges. Tumor immune–metabolic reprogramming profoundly affects treatment response and immune evasion; however, the molecular mechanisms of lipid metabolism remodeling and its interaction with T cells after CCRT in cervical cancer are still unclear. This study aimed to investigate how CCRT-induced metabolic changes in cervical cancer cells influence T cell function and immune evasion. Methods: We performed metabolic pathway activity analysis, cell–cell communication prediction, and transcriptomic analysis on paired single-cell transcriptomic data from three cervical cancer patients before and after CCRT (n = 3 paired). Validation was conducted using multiple independent GEO cohorts, in vitro cell culture experiments, and multi-sample immunofluorescence staining. Results: CCRT was associated with upregulation of FABP4/5 in malignant epithelial cells and activation of the PPAR and adipocytokine signaling pathways, leading to lipid metabolic reprogramming. Epithelial cells with high FABP4/5 expression showed enhanced predicted intercellular communication with T cells via the computationally inferred ligand–receptor axes PTGER4 and CXCR4. T cells with high communication intensity exhibited an immunosuppressive phenotype signature, accompanied by metabolic alterations in lipid and carbohydrate pathways and enrichment of regulatory T cell subsets. Validation experiments confirmed the association between FABP4/5 and inhibitory T cells. Conclusions: This study suggests that FABP4/5-mediated lipid metabolism reprogramming may represent a key mechanism contributing to the immunosuppressive crosstalk between cervical cancer epithelial cells and T cells after CCRT. Targeting this axis may reverse T cell dysfunction and provide a potential immunometabolic strategy to reduce post-CCRT recurrence. Full article

Lung cancer is classified as either Non-Small Cell (NSCLC) and Small Cell Lung Cancer (SCLC) and still represents the leading cause of cancer-related mortality worldwide. Prognosis of NSCLC and SCLC patients is grim; thus, novel therapies are needed. In this context, plant-derived compounds, such as olive leaf extract (OLE), recently attracted much interest for their anti-cancer properties. We investigated the impact of OLE on cell proliferation and apoptosis (by flow cytometry) and migration (by scratch test and transwell assay) of NSCLC and SCLC cell lines, underlying the mechanisms involved. Synergistic effects with cisplatin were also evaluated. OLE differentially impaired cell proliferation and induced apoptosis in LC cell lines. Notably, such effects were higher in SCLC than in NSCLC cell lines. Further analyses were performed on GLC-1 and SKMES cells, identified as OLE-sensitive and OLE-resistant models, respectively. Indeed, OLE triggered the intrinsic apoptotic pathway by activating cleaved caspase-9, -3 and -7, and induced DNA damage response and cellular stress molecules in GLC-1 cells only. In contrast, OLE affected migratory capacity of SKMES cell line and modulated stress adaptation and survival pathways. Finally, OLE synergized with cisplatin in the induction of apoptosis in GLC-1 cells. OLE exerted multiple anti-tumor effects on LC cells in vitro. Its ability to enhance cisplatin-induced apoptosis supports further investigation of OLE as a potential dietary adjunct to chemotherapy. Although OLE has an established safety profile, in vivo studies are required to validate its efficacy, and assess potential interactions with chemotherapeutic drugs before any clinical application. Full article

Following the first approval for prostate cancer (PCa) treatment of competitive antagonists of the androgen receptor (AR) function that bind to the androgen-binding pocket, much progress has been achieved regarding compound efficacy and specificity. Second-generation compounds and androgen synthesis blockers are now standard-of-care AR pathway inhibitors given to PCa patients. More recently, approaches targeting AR regions other than the ligand-binding domain (LBD), stimulating proteasome-mediated AR degradation, or bringing together the AR with an effector protein (EP) in prostate tumor cells, have been explored and, in several cases, clinically tested. Compounds blocking AR mRNA splicing or directly addressing AR splice variants, especially the constitutively active AR-V7 form, are also being evaluated. In addition, there are ongoing efforts aiming at impairing the function of essential AR cofactors, mainly those involved in downstream gene transcription and chromatin modulation. Alternative techniques to impair AR activity, such as nanoparticle formulations and targeting biomolecular condensates are furthermore being explored. Here we present the most recent developments in these different strategies to target the AR, directly or indirectly, for a more potent and long-lasting blockade. This will hopefully soon lead to treatments that improve progression-free and overall survival in PCa patients, while maintaining a good safety profile. Full article

Metastatic androgen pathway modulation-resistant (mAPMR) prostate cancer subtypes harboring androgen receptor (AR) alterations have distinct AR biology that may impact response to therapy. We hypothesized that patients harboring AR T878A would have superior responses to AR pathway inhibitor (ARPI) therapy based on prior preclinical data. We utilized a large genomic-clinical database to identify mAPMR patients with AR T878A, AR L702H and AR amplification and performed a matched assessment of ARPI treatment outcomes using real-world surrogate endpoints for treatment response. Among AR T878A patients treated with enzalutamide, time to treatment discontinuation (TTD) was longer relative to patients with AR L702H (8 mo (95% CI 4.6–44 mo) vs. 3.5 mo (95% CI 2.3–5.5 mo) log-rank p < 0.0001) or AR amplification (7.7 mo (95% CI 4.7–15.8 mo) vs. 4.8 mo (95% CI 4–5.1 mo) (log-rank p = 0.0034). Among the AR T878A patients treated with abiraterone, TTD was not significantly different relative to patients with AR L702H, but longer relative to patients with AR amplification (7.1 mo (95% CI 5–8.5 mo) vs. 4.2 mo (95% CI 3.5–5.4 mo) (log-rank p = 0.037). This study provides hypothesis generating evidence that outcomes for patients with AR LBD mutations may differ by mutation subtype. AR T878A may be relatively more sensitive to ARPI treatment than AR L702H or amplified AR. Full article

KRAS is one of the most frequently altered oncogenes in non-small cell lung cancer (NSCLC), playing a pivotal role in tumour initiation, progression, and therapeutic response. This review summarises the current understanding of the molecular mechanisms underlying KRAS-driven NSCLC, with particular emphasis on signalling pathways, genetic alterations, and their clinical implications. We discuss the spectrum of KRAS mutations and polymorphisms, highlighting their impact on disease biology, prognosis, and treatment outcomes. In addition, the review explores the contribution of epigenetic regulation to KRAS-mediated oncogenesis, focusing on the roles of non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), as well as post-translational modifications of the KRAS protein, such as methylation, phosphorylation, ubiquitination, nitrosylation, and acetylation. Recent advances in the development of KRAS-targeted therapies are presented, including mutation-specific and pan-KRAS inhibitors. Furthermore, we discuss combination treatment approaches designed to overcome intrinsic and acquired resistance by targeting complementary signalling pathways or modulating the tumour microenvironment. Collectively, this review highlights the complexity of KRAS biology in NSCLC and underscores the importance of integrating molecular, epigenetic, and therapeutic insights to advance precision medicine and improve clinical outcomes. Full article

Background: Mpp46Aa1 (formerly PS2Aa1) is a β-pore-forming protein produced by Bacillus thuringiensis that exhibits selective cytotoxicity against cancer cells. Protein engineering has generated variants with improved antitumor activity, including the N65 variant, which contains three amino acid substitutions. Objective: In this study, three individual reversion variants of N65 were generated by site-directed mutagenesis to determine the contribution of each substitution to cytotoxicity, selectivity, and cell death mechanisms in the colorectal cancer cell lines SW480 and SW620 and the non-tumorigenic colonic epithelial cell line NCM460. Methods: Recombinant proteins were purified and evaluated using AlamarBlue viability assays, Annexin V/Cy3 staining, caspase-3/7 and caspase-9 activation assays, and JC-1 mitochondrial membrane potential analysis. Results: The reversion variants differentially affected the biological activity of N65. Among them, the D34N variant exhibited low IC₅₀ values against both colorectal cancer cell lines, while maintaining selectivity towards non-cancerous cells. D34N also induced phosphatidylserine externalization, activation of caspase-3/7 and caspase-9, and mitochondrial membrane depolarization, indicating activation of the intrinsic apoptotic pathway. Structural analyses revealed that the reverted residues modified local interaction networks, suggesting that these positions may influence CD59 recognition and contribute to cellular selectivity. Conclusions: These findings demonstrate that the three substitutions present in N65 contribute unequally to its biological activity and identify residue 34 as a key determinant of Mpp46Aa1 cytotoxicity. This study provides structural and functional insights that support the rational engineering of parasporins with enhanced antitumor selectivity. Full article

Frailty, cognitive impairment, depression, functional dependency, low physical performance, and undernutrition are highly prevalent in older adults referred for cancer treatment, cardiovascular interventions, neurological therapies, and orthopaedic surgery, and each independently predicts treatment toxicity, post-procedural complications, and mortality. Comprehensive Geriatric Assessment (CGA) is the most accurate predictor of treatment outcomes in older patients, yet it remains structurally absent from most speciality pathways, contributing to overtreatment of biologically frail patients and undertreatment of biologically robust ones. In this Viewpoint, we propose and operationalise the FIT–FRAIL–DISABLE multidimensional geriatric stratification model as a conceptual framework for translating CGA findings into proportional, speciality-specific treatment recommendations across oncology, cardiology, neurogeriatrics, and orthogeriatrics. The model integrates six validated CGA instruments—the Mini-Mental State Examination (MMSE), the 15-item Geriatric Depression Scale (GDS-15), basic and instrumental Activities of Daily Living (ADL, IADL), the Short Physical Performance Battery (SPPB), and the Mini Nutritional Assessment Short Form (MNA-SF)—into three actionable categories (FIT, FRAIL, DISABLE) aligned with full-intensity, risk-adapted, and symptom-focused care, and is explicitly positioned in relation to the deficit-based frailty paradigm and the WHO Intrinsic Capacity (ICOPE) framework, which it complements rather than replaces. We specify a provisional, a priori decision rule for combining domain scores and describe how each stratification category should inform—but not dictate—goal-concordant treatment intensity within a shared decision-making process. FIT–FRAIL–DISABLE is presented as a proposed, hypothesis-generating framework: its composite thresholds and domain weighting have not yet been empirically derived, and the model has not undergone prospective validation. Retrospective calibration on existing CGA cohorts and prospective multicentre validation are being designed within the GERIA-NET research consortium. If validated, the framework has the potential to reduce both overtreatment-related harm and undertreatment-related therapeutic deprivation in older adults undergoing active treatment. Full article

The intestinal microbiome has emerged as a clinically significant modulator of outcomes across multiple domains of cancer care. In hematopoietic stem cell transplantation (HSCT), loss of microbial diversity and depletion of short-chain fatty acid-producing commensals are independently associated with graft-versus-host disease (GvHD), bloodstream infections, transplant-related mortality, and overall survival. Mechanistic studies have identified interconnected pathways—including butyrate-mediated epithelial protection, tryptophan-derived aryl hydrocarbon receptor signaling, bile acid metabolism, and Paneth cell–intestinal stem cell interactions—through which microbial communities regulate intestinal barrier integrity and immune homeostasis. These insights have provided the biological rationale for therapeutic strategies aimed at restoring microbial ecology. Fecal microbiota transplantation (FMT) has demonstrated promising clinical activity in steroid-refractory acute GvHD, with one meta-analysis reporting a pooled clinical remission rate of 64% (95% CI, 51–77%) across prospective single-arm studies, and proprietary live biotherapeutic products (LBPs) such as MaaT013 met the primary endpoint of the single-arm phase III ARES trial, achieving a day-28 gastrointestinal overall response rate of 62%; however, the CHMP adopted a negative opinion on its conditional marketing authorization application in June 2026, citing limitations of the single-arm design, and a re-examination is pending. In parallel, gut microbiome composition has been associated with immune checkpoint inhibitor (ICI) response, and early-phase FMT studies suggest that microbiome modulation may restore sensitivity to anti-PD-1 therapy in some patients with refractory melanoma and may enhance treatment responses in first-line ICI settings; however, these findings derive primarily from small, uncontrolled or early-phase studies. Defined single-strain approaches, notably Clostridium butyricum MIYAIRI 588 (CBM588), have shown encouraging secondary clinical efficacy signals in two small, randomized phase I trials in metastatic renal cell carcinoma, including significantly prolonged progression-free survival in one trial and a higher objective response rate in another; however, neither trial met its prespecified primary microbiome endpoint of increased Bifidobacterium spp. abundance. Emerging evidence further links antibiotic-induced dysbiosis to impaired chimeric antigen receptor T-cell (CAR-T) therapy outcomes, while short-chain fatty acids have been identified as direct enhancers of CAR-T cell effector function. This review synthesizes the current evidence for microbiome-based therapeutics across HSCT, GvHD, ICI therapy, CAR-T cell therapy, and infection prevention, and addresses cross-cutting translational challenges including antibiotic stewardship, donor selection, safety in immunocompromised populations, and pharmacomicrobiomics. While randomized controlled trial data remain limited and many approaches are investigational, the convergence of mechanistic, observational, and early interventional evidence positions microbiome restoration as a promising frontier in precision oncology. Full article

Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Increasing evidence suggests that intestinal microbial dysbiosis contributes to colorectal tumorigenesis by reshaping host molecular signaling and the tumor immune microenvironment. However, the molecular mechanisms linking microbiome-associated alterations to host regulatory networks and disease progression remain incompletely understood. Objective: This study aimed to identify the microbiome-associated molecular regulators and immune modulators involved in colorectal cancer through an integrative multi-omics systems biology approach. Methods: Publicly available transcriptomic datasets were analyzed to identify differentially expressed genes, followed by functional enrichment, protein-protein interaction network construction, hub gene prioritization, immune infiltration profiling, survival analysis, and multi-omics characterization. Results: The identified hub genes represent hypothesis-generating host candidates for further mechanistic and clinical validation. These genes occupied key positions within host regulatory networks and were significantly associated with adverse clinical outcomes and altered CD8⁺ T-cell infiltration, suggesting their involvement in immune remodeling within the tumor microenvironment. Multi-omics characterization demonstrated that PTEN and SMAD4 alterations were predominantly associated with genomic deletions, whereas SMAD2 dysregulation was associated with transcriptomic and gene-dosage variation. Although the overall mutational burden of the identified hub genes was not significantly associated with disease-free survival (p = 0.878), these molecular regulators showed associations with immune-cell infiltration and CRC-related pathways. Conclusions: Collectively, our findings provide a system-level framework describing the associations between dysbiosis-relevant host pathways, CRC-related regulatory networks, and immune responses. Full article

Automated prostate cancer (PCa) lesion segmentation using deep learning remains constrained by limited tissue contrast in standard diffusion-based MRI sequences, with state-of-the-art methods reporting Dice scores of 32% or lower on large patient cohorts. Synthetic correlated diffusion imaging (${\mathrm{CDI}}^s$) offers a promising solution, providing enhanced tissue contrast derived entirely from existing diffusion-weighted imaging (DWI) acquisitions at no additional clinical cost. This study presents the first comprehensive evaluation of ${\mathrm{CDI}}^s$ integration across the full standard multiparametric MRI protocol, encompassing 15 modality configurations and six segmentation architectures spanning CNN and transformer families on a cohort of 200 patients. ${\mathrm{CDI}}^s$ reliably enhances or preserves segmentation performance in the evaluated configurations, with 19 statistically significant improvements and no significant degradations across 42 direct comparisons. ${\mathrm{CDI}}^s$ enhancement primarily operates as a recall-driven mechanism, improving lesion detection sensitivity while largely preserving precision. ${\mathrm{CDI}}^s$ + DWI + T2w emerged as the strongest clinically meaningful configuration, achieving significant Dice improvement in four of six architectures, with no instances of degradation. Grad-CAM-based explainability analysis further reveals that ${\mathrm{CDI}}^s$ focuses poorly localized CNN attention toward lesion boundaries, while transformer architectures exhibit more stable attention patterns that are less sensitive to ${\mathrm{CDI}}^s$ integration. These results establish validated ${\mathrm{CDI}}^s$ integration pathways and provide architecture-specific deployment guidance for clinical implementation. Full article

Cutaneous melanoma remains a global health challenge. Although BRAF/MEK-targeted therapies and immune checkpoint inhibitors (ICIs) have improved outcomes in advanced disease, durable responses remain difficult to achieve for most patients. Therapeutic resistance represents the central barrier to long-term disease control. This review comprehensively examines the molecular and immunologic mechanisms underlying melanoma resistance and integrates these insights with emerging pharmaceutical strategies designed to overcome them. We explore the genetic landscape of melanoma, including oncogenic alterations in BRAF, NRAS, NF1, CDKN2A, and PTEN, and explain how dysregulation of the MAPK and PI3K/AKT/mTOR signaling axes drives therapeutic escape. Phenotypic plasticity is discussed as a critical epigenetic driver of drug tolerance. The tumor microenvironment (TME) is examined as an active co-conspirator in resistance, encompassing immunosuppressive cell populations, cancer-associated fibroblasts, and metabolic competition. Resistance mechanisms to targeted therapy, including MAPK reactivation, bypass signaling, transcriptional reprogramming, and metabolic rewiring, are reviewed alongside tumor-intrinsic and tumor-extrinsic mechanisms of ICI resistance. Emerging therapeutic strategies are surveyed, including next-generation RAF and ERK inhibitors, dual-pathway blockade, and metabolic therapies targeting oxidative phosphorylation. Innovations in molecular imaging, liquid biopsy, and artificial intelligence-driven biomarker discovery are highlighted as pivotal tools for real-time resistance monitoring and adaptive treatment. By linking mechanistic insights with translational advances, this review advocates for combination strategies and adaptive clinical frameworks to achieve more durable disease control in melanoma. Full article

Background: Pancreatic cancer cells adapt to nutrient stress by activating metabolic pathways that facilitate survival and proliferation within the tumor microenvironment, a phenomenon known as austerity. Targeting this resilience presents a strategy for developing chemotherapeutic agents with anti-austere properties. Methods: Phytochemical investigation of Nelumbo nucifera petals led to the isolation of six alkaloids: three benzylisoquinolines (1–3), two aporphines (4, 5), and one proaporphine (6). Preferential cytotoxicity under nutrient deprivation was evaluated. The most active compound was further analyzed in MIA PaCa-2 cells using proliferation, migration, colony formation, and three-dimensional spheroid growth assays, with additional selective cytotoxicity assessment in KLM-1 cells. Mechanistic studies examined MAPK family signaling, autophagy-associated alterations, and apoptosis. Results: (−)-N-nornuciferine (5) exhibited considerable preferential cytotoxicity against MIA PaCa-2 cells (PC₅₀ = 0.53 µM) and KLM-1 cells (PC₅₀ = 1.11 µM). Under nutrient-rich conditions, 5 suppressed the proliferation, migration, colony formation, and spheroid growth of MIA PaCa-2 cells. Under nutrient deprivation, 5 increased MAPK phosphorylation and LC3-II accumulation while reducing p62/SQSTM1 levels. Chloroquine (CQ) further increased LC3-II accumulation, particularly at 10 µM 5, compared with CQ alone. However, autophagy inhibitors did not rescue 5-induced loss of viability, and the pan-caspase inhibitor Z-VAD-FMK also failed to significantly mitigate cytotoxicity. No detectable PARP or caspase-3 cleavage was observed. Conclusions: (−)-N-nornuciferine (5) exhibits anti-austere and anticancer activities in pancreatic ductal adenocarcinoma (PDAC) models, accompanied by MAPK phosphorylation and autophagy-related changes under nutrient deprivation conditions. Conventional caspase-dependent apoptosis is unlikely to be the main contributor to this process. Full article