Search Results (834)

Background: Endobronchial ultrasound (EBUS) is widely used for the diagnosis of pulmonary lesions. When combined with rapid on-site cytologic evaluation (ROSE), it can improve diagnostic accuracy and facilitate early identification of malignancy origin. However, differentiating primary lung cancer from metastatic tumors (e.g., breast or colorectal origin) during ROSE remains challenging due to limited cytopathology support and morphological similarities between tumor cells. This study aimed to develop a computer-aided diagnostic (CAD) system for classifying malignancy types from limited cytological samples to facilitate clinical decision-making. Methods: We utilized a retrospective dataset of cytological images obtained during EBUS procedures between November 2018 and June 2024. The study focused on classifying three malignancies: pulmonary adenocarcinoma, metastatic breast cancer, and metastatic colorectal cancer. A deep learning-based model (PLFCH) was developed, integrating few-shot learning, parameter-efficient fine-tuning, and a hybrid CNN–Transformer architecture to address limited annotated data. Results: A total of 41 patients with 346 cytological images were included. Under a 3-way 5-shot setting, the proposed model achieved an accuracy of 49.26%, outperforming existing few-shot learning methods, with precision, recall, and F1-score of 0.477, 0.493, and 0.480, respectively. Increasing the number of reference images to 20 per class further improved accuracy to 55.48%. Conclusions: The proposed framework demonstrated improved performance for cytological classification under limited data conditions. These findings provide an early proof of concept for applying few-shot learning to cytological assessment during EBUS procedures. Further improvements in model performance and validation in prospective, real-time clinical settings are required before its potential role in assisting diagnostic decision-making can be established. Full article

Background/Objectives: Although paraprobiotics and postbiotics may beneficially affect glucose metabolism, their direct influence on intestinal glucose transporters remains poorly understood. This study investigated the in vitro effects of selected heat-killed Lactobacillaceae strains and cell-free supernatants from their viable counterparts on sodium-driven glucose cotransporter 1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) expression and basolateral glucose accumulation. Methods: Experiments were performed using non-carcinogenic porcine-derived enterocytes (CLAB) and human epithelial colorectal adenocarcinoma cells (Caco-2; ATCC HTB-37). SGLT1 and GLUT2 gene and protein expression, as well as basolateral glucose concentration after a 6-hour incubation, were assessed. Results: Heat-killed probiotics and cell-free probiotic supernatants generally increased SGLT1 protein expression in both cell models, except for heat-killed Lactobacillus acidophilus. In contrast, GLUT2 modulation differed between cell models and treatments. In CLAB cells, GLUT2 protein levels were generally reduced, particularly following exposure to cell-free probiotic supernatants, whereas responses in Caco-2 cells were less consistent. Treatment-dependent changes in basolateral glucose concentration and 6-h net basolateral glucose accumulation were also observed, with significant effects for selected heat-killed strains in CLAB cells. Conclusions: Lactobacillaceae-derived heat-killed preparations and cell-free supernatants may differentially modulate intestinal glucose transporter expression in a strain- and cell-model-dependent manner. However, changes in transporter expression and basolateral glucose accumulation do not establish a transporter-specific glucose flux or mechanism. Further mechanistic studies using complementary intestinal models are required to clarify these effects and their translational relevance. Full article

Immune checkpoint blockade has changed the management of several digestive system cancers, but its impact is highly context dependent. This review evaluates evidence for esophageal, gastric and gastroesophageal junction, colorectal, hepatocellular, biliary tract and gallbladder, and pancreatic cancers. Randomized phase III trials have established chemoimmunotherapy or dual-checkpoint strategies in advanced esophageal cancer, biomarker- and regimen-dependent first-line therapy in gastric cancer, PD-1-based therapy for MSI-H/dMMR colorectal cancer, atezolizumab–bevacizumab and STRIDE for unresectable hepatocellular carcinoma, and chemoimmunotherapy for advanced biliary tract cancer. Recent results also expand perioperative treatment: neoadjuvant checkpoint blockade produces high pathological response rates in dMMR colon cancer, adjuvant atezolizumab plus mFOLFOX6 improves disease-free survival in stage III dMMR colon cancer, and perioperative serplulimab improves event-free survival in PD-L1-positive resectable gastric cancer. These advances coexist with important negative findings. Pembrolizumab-containing therapy did not meet superiority end points in KEYNOTE-062, the initial adjuvant signal in IMbrave050 was not sustained, and unselected pancreatic ductal adenocarcinoma remains largely resistant to checkpoint blockade. Early vaccine, cellular, TIGIT, radiomics, spatial, and multi-omics studies remain hypothesis-generating and require external or randomized validation. Clinical interpretation should integrate evidence maturity, biomarker validity, immune-related toxicity, patient-reported outcomes, cost, access, and manufacturing demands rather than response rate alone. Full article

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related mortality worldwide. Although screening has reduced CRC in older adults, cases in younger individuals are rising, highlighting the need for early biomarkers. Emerging research highlights the role of estrogen metabolism in CRC progression, with enzymes such as hydroxysteroid (17-beta) dehydrogenase (HSD17B) being increasingly implicated. In this study, we performed a bioinformatics analysis using publicly available datasets, including The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort and two independent Gene Expression Omnibus (GEO) cohorts (GSE40967 and GSE41258), to investigate the role of HSD17B enzymes in CRC. Our results suggest that HSD17B2 is frequently downregulated in precancerous lesions and early-stage CRC, which may contribute to elevated estradiol levels and a tumor-promoting microenvironment. In advanced stages, higher HSD17B2 expression levels are associated with poorer survival outcomes in retrospective cohorts. Other HSD17B enzymes also exhibit significant expression changes, further complicating the hormonal landscape of CRC. In addition, estrone, traditionally considered a weaker estrogen, emerges as a potential driver of CRC progression. Our in-silico analyses indicate that HSD17B2 and HSD17B11 warrant further investigation as candidate biomarkers for distinguishing CRC from benign and precancerous conditions, with the combination showing strong discriminatory power in Receiver Operating Characteristic (ROC) analyses. Overall, these findings highlight the potential role of estrogen metabolism in CRC and suggest that HSD17B enzymes may hold value as candidate prognostic and diagnostic indicators, though their clinical utility remains hypothetical at this stage. Experimental and clinical validation is strictly required to confirm these in silico observations and to clarify their mechanisms in CRC. Full article

Species belonging to the genus Seseli have long been known to be used as herbal remedies in traditional medicine for various purposes such as colds, inflammation, pain, and gastrointestinal disorders. Therefore, in this study, the flower parts of Seseli transcaucasicum (Schischk.) Pimenov & Sdobnina were extracted using methanol and acetone to investigate their phytochemical composition and antioxidant, antimicrobial, and cytotoxic activities. For this purpose, total phenolic content (TPC), DPPH free radical scavenging activity (RSA), phenolic component (PCs) profile, volatile component composition, antimicrobial effect, and cytotoxic potential on the HT29 human colorectal adenocarcinoma cell line were evaluated. When the results were examined, HPLC analysis of phenolic components revealed that both extracts contained particularly high levels of rosmarinic acid, catechin, and quercetin. Among these, rosmarinic acid was detected in the highest amount, with 15.195 mg/g in the methanol extract and 14.929 mg/g in the acetone extract. The volatile components of this plant were determined by GC-MS, and a total of 29 volatile compounds were identified. Among these, β-pinene (220.792 mg/kg), Δ3-carotene (81.898 mg/kg), α-sedrene (63.331 mg/kg), elixen (44.535 mg/kg), sabinene (40.822 mg/kg), and D-limonene (38.422 mg/kg) were identified as the most dominant compounds. It was observed that the methanol extract had a higher total phenolic content (77.389 ± 1.389 mg gallic acid equivalent/g extract) and higher free radical scavenging activity (40.933 ± 0.067 mg trolox equivalent/g extract) compared to the acetone extract. Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans strains were used to determine the antimicrobial activities of plant extracts, and moderate inhibitory effects were observed against these microorganisms. The highest antimicrobial activity was determined by the 16 mm inhibition zone created against S. aureus by the methanol extract at a concentration of 100 mg/mL. The cytotoxic activity of the plant was determined by measuring its dose-dependent antiproliferative effect on HT29 cells. When the difference between solvents was examined, it was observed that the acetone extract at a concentration of 500 µg/mL reduced cell viability by 18.03%, while the methanol extract at the same concentration reduced viability by 30.56%. According to the results, S. transcaucasicum is rich in phenolic and terpenic compounds and exhibits antioxidant, antimicrobial, and cytotoxic effects. Therefore, this plant species is considered a promising resource for the development of naturally occurring biologically active compounds. Full article

Epilobium parviflorum Schreb. is a medicinal plant used traditionally against inflammatory disorders whose cytotoxic potential is still incompletely revealed. The current study investigates the phytochemical composition and in vitro cytotoxic activity of four hydroalcoholic extracts prepared from the aerial parts of E. parviflorum by using maceration and Soxhlet extraction. The extracts were characterized in terms of total phenolic, flavonoid and tannins composition and LC-MS was used to identify its individual polyphenols. Their biological effects were assessed against four cancer cell lines (A375 melanoma, HT-29 colorectal adenocarcinoma, PANC-1 pancreatic carcinoma and SK-OV-3 ovarian adenocarcinoma cells), while using HaCaT keratinocytes as healthy cells in order to assess selectivity. Cell viability, cytoskeletal and nuclear morphology, mitochondrial respiration and network pharmacology were further investigated. A complex phenolic profile was revealed, with hyperoside being identified as the main component in all extracts while the extraction parameters strongly influenced the recovery of various phenolic compounds. All extracts reduced cancer cell viability in a dose-dependent manner after 24 h exposure, with the most pronounced effects observed at 720 and 1000 μg/mL, while HaCaT cells were left relatively unaffected. The morphological assessment indicated nuclear condensation, fragmentation and cytoskeletal disruption following the application of extracts. Moreover, high-resolution respirometry showed reduced oxidative phosphorylation and electron transfer system capacity thus indicating that early mitochondrial dysfunction may contribute to the cytotoxic effects. Network pharmacology revealed that ERBB2, CTNNB1, HSP90AA1 and HDAC6 might act as molecular targets in melanoma. Thus, these findings support the hypothesis that E. parviflorum hydroalcoholic extracts, particularly the 40% ethanol Soxhlet extract, may serve as important sources of bioactive phytocompounds with antiproliferative and apoptotic properties. Full article

Protease-activated receptor-2 (PAR-2; encoded by F2RL1) is emerging as a context-dependent driver of gastrointestinal cancer. Activated by irreversible N-terminal cleavage, its signalling output is not fixed but is calibrated by the identity and source of the activating protease, the receptor cleavage state, cellular context and biased coupling to G-protein αq (Gαq), G-protein α12/13 (Gα12/13) and β-arrestin. PAR-2 is best understood not as a simple inflammatory receptor but as a proteolytic rheostat that converts diverse coagulation, inflammatory, microbial and stromal protease inputs into distinct oncogenic programmes. Colorectal cancer and pancreatic ductal adenocarcinoma provide complementary models: in colorectal cancer, PAR-2 links mucosal inflammation and coagulation to proliferation, metastatic competence and resistance to epidermal growth factor receptor (EGFR)-targeted therapy, whereas in pancreatic cancer, it is embedded in a tissue-factor-rich desmoplastic microenvironment that promotes invasion, immune exclusion and chemoresistance. Therapeutic strategies suggested by this framework include direct and biased PAR-2 modulators, upstream protease and factor Xa (FXa) inhibition, statin repurposing and activated-fragment biomarkers such as the PAR-2 activation neoepitope (PRO-PAR2). These strategies must be applied under biomarker guidance, since PAR-2 blockade may benefit inflammation-dominant tumours yet prove counterproductive where PAR-2 sustains antitumour immunity. Full article

Preoperative immunonutritional indices are widely reported to predict survival after colorectal cancer (CRC) resection, yet their independence varies across cohorts and no data exist from the Arab Gulf. In this retrospective cohort study we analyzed 316 patients undergoing curative resection for stage I–III colorectal adenocarcinoma at a Saudi tertiary center between 2013 and 2022, of whom 48 (15.2%) presented as emergencies. The prognostic nutritional index (PNI) and a composite albumin–neutrophil-to-lymphocyte ratio (albumin–NLR) score were assessed against overall survival (OS) and disease-free survival (DFS) using Cox models adjusted for age, sex, emergency presentation, tumor site, neoadjuvant therapy, adjuvant chemotherapy and lymphovascular invasion and stratified by stage and American Society of Anesthesiologists class. Over a median follow-up of 58.1 months there were 88 deaths and 124 DFS events. The PNI independently predicted OS (adjusted hazard ratio 0.958, 95% CI 0.929–0.987) and DFS (0.964, 0.940–0.988); the albumin–NLR score did not. Albumin alone carried the signal (OS 0.938), with lymphocytes, neutrophils and the NLR all null. The PNI effect was confined to the first 36 months (0.944 versus 1.003 thereafter), and published cut-offs classified 70.8% of the cohort as high-risk. Immunonutritional prognostication in CRC is albumin-driven, time-limited and sensitive to cut-off provenance. Full article

Colorectal cancer is a leading cause of cancer death, yet its molecular heterogeneity remains poorly translated into individualized treatment. We present a reproducible artificial intelligence (AI) framework that integrates multi-omics benchmarking, sample-level drug prioritization, E3 ubiquitin ligase selection, and shape-anchored Proteolysis Targeting Chimera (PROTAC) design for KRASG12D in colon adenocarcinoma (COAD). A controlled synthetic benchmark comprising 425 tumor and 41 simulated normal profiles, parameterized to match The Cancer Genome Atlas (TCGA) distributions, was used for pipeline verification. Among sixteen methods, the Balanced Latent Integration with Stability Selection (BLISS) model achieved the highest silhouette width (0.86) and competitive agreement (Adjusted Rand Index, ARI, 0.90). The pipeline was validated on real data: a TCGA COAD cohort (186 tumors) with independent Consensus Molecular Subtype (CMS) labels and a CPTAC cohort (104 tumors). Integration modestly recovered CMS (ARI 0.28), and stage, not molecular cluster, drove survival (log-rank p = 0.005 versus 0.81). Sample-level prioritization differed from cluster-level ranking in 82.6% of profiles, below chance (p < 0.0001), without indicating efficacy. Candidate NOVEL00489 showed a good MM-GBSA estimate, matching the reference ASP3082. Compounds are computational candidates requiring experimental validation. This establishes a transparent benchmark for in silico degrader generation in precision oncology. Full article

A hard protein corona was engineered onto tannic acid-modified magnetic nanoparticles (SAMN@TA), a magnetic and luminescent core–shell nano-carrier, using bovine serum amine oxidase (BSAO), an enzyme catalyzing the oxidation of polyamines and producing the corresponding aldehydes and hydrogen peroxide. The absorption and intracellular bioactivity of the self-assembled multimodal SAMN@TA@BSAO were investigated on an intestinal barrier model built with human colorectal adenocarcinoma (Caco-2) cells. The tailored BSAO corona possessed fouling resistance and, at the same time, was able to activate the clathrin-mediated endocytosis (CME) mechanism. Despite its size and intrinsic complexity, the nano-vehicle was effectively transported across the cell layer, safely transiting across the cell cytoplasm and reaching the lumen. As a function of intracellular polyamine concentration, the system’s biological activity induced intracellular oxidative stress, leading to the activation of the Keap1/Nrf2 oxidative protection pathway. The SAMN@TA@BSAO effect was well described by a dose–response curve with an EC₅₀ of around 30 µg mL⁻¹ and a programmable killing efficiency (>50.0%), recalling the feasibility of a low molecular weight drug administration. The present study contributes to the nascent knowledge on engineering protein corona as a key to rationally design nanomaterials for biomedical applications. Full article

Approximately 30% of tumors contain an activating mutation in the oncogene KRAS, leading to increased cell proliferation that often promotes non-small cell lung cancers, colorectal adenocarcinomas, pancreatic ductal adenocarcinomas (PDAC), and other cancers. Among the most common point mutations in KRAS is G12D, an example of an oncogenic sequence present in tumor cells but not normal cells. We developed peptide nucleic acid (PNA) oligomers that selectively bind KRAS G12D sequences and fused them with novel cell-penetrating peptide flanking regions (CPP-PNA-G12D) then evaluated them. Electrophoretic mobility shift assays demonstrated in vitro binding to and selectivity for KRAS G12D over wild-type KRAS and KRAS G12C. Cells and nuclei were able to uptake CPP-PNA-G12D at high efficiency as shown by fluorescent microscopy and flow cytometry. Cell viability assays showed a striking dose-response effect in on-target cells expressing KRAS G12D, while relatively sparing off-target cells expressing KRAS G12C. CPP-PNA-G12D constructs were effective against a panel of PDAC cell lines and in female Balb/c mice bearing patient-derived xenografts. These results show promise for an enhanced PNA-delivery peptide conjugate strategy as a potential therapeutic strategy to selectively target KRAS mutant cancer cells, with the potential to expand this technology to additional cancer-derived mutant oncogenes. Full article

Pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) are aggressive malignancies frequently driven by oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations associated with metabolic reprogramming and resistance to apoptosis. In this study, we evaluated the antitumor and anti-inflammatory activity of a Lepidium latifolium L.-derived formulation (CTP) enriched in glucosinolate hydrolysis products in KRAS-mutant colorectal and pancreatic cancer models. The formulation was designed to promote the generation of the epithionitrile 1-cyano-2,3-epithiopropane (CETP) through iron-dependent myrosinase-mediated sinigrin hydrolysis. CTP induced dose-dependent cytotoxicity and morphological alterations consistent with apoptosis in KRAS-mutant cancer cell lines. Treatment significantly reduced mitochondrial membrane potential, ATP production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR), indicating severe bioenergetic impairment. In parallel, CTP downregulated the metabolic and proliferative regulators C-myc, PKM2, GLUT1, and Cyclin E1. RNA-seq analysis revealed extensive transcriptional reprogramming associated with oxidative stress, metabolic adaptation, and cell-cycle regulation. In addition, CTP significantly suppressed nitric oxide, IL-6, and IL-8 production in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that glucosinolate-derived metabolites from L. latifolium interfere with metabolic and inflammatory pathways critical for KRAS-driven tumor survival and support the therapeutic potential of Brassicaceae-derived epithionitriles as multitarget anticancer agents. Full article

Background: Metabolic reprogramming enables cancer cells to adapt to energetic stress and sustain proliferation. Simultaneous inhibition of glycolysis and mitochondrial respiration has emerged as a promising strategy to overcome metabolic plasticity. This study evaluated the antiproliferative effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) alone and in combination with metformin in human cancer cell lines. Methods: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), colorectal adenocarcinoma (HT-29), and normal lung fibroblasts (MRC-5) were treated with 2-DG or metformin individually, or with metformin in the presence of a fixed concentration of 2-DG (1 mM). Cell viability was assessed using the sulforhodamine B assay after 24 and 48 h. IC₅₀ values were calculated by nonlinear regression, Dose Reduction Index (DRI) analysis evaluated sensitization to metformin, and molecular docking was performed to investigate interactions with selected metabolic targets. Results: Both 2-DG and metformin inhibited cell proliferation in a concentration- and time-dependent manner. HeLa cells were the most sensitive to glycolytic inhibition, while A549 and HT-29 cells showed moderate susceptibility. Co-treatment with 2-DG significantly enhanced metformin activity, reducing its IC₅₀ in HeLa cells from 6.04 to 2.00 mM after 24 h and from 2.28 to 1.56 mM after 48 h. DRI analysis demonstrated increased sensitivity to metformin in all cancer cell lines, particularly HT-29 and A549, whereas normal MRC-5 fibroblasts remained comparatively less affected. Molecular docking revealed favorable binding of both 2-DG and metformin to proteins involved in cellular energy metabolism. Conclusions: Combined inhibition of glycolysis and mitochondrial respiration potentiates the antiproliferative effects of metformin, increases metabolic vulnerability in cancer cells, and is supported by molecular docking evidence of interactions with metabolic targets, while showing limited toxicity toward normal fibroblasts. These findings support dual metabolic targeting as a promising therapeutic strategy and warrant further mechanistic and in vivo studies. Full article

Background: The role of primary tumor resection (PTR) in patients with de novo stage IV colorectal cancer remains controversial, particularly in the context of patient selection and tumor biology. This study aimed to evaluate the association between PTR and survival outcomes and to identify clinical, molecular, and inflammatory-nutritional prognostic factors in patients with de novo stage IV colorectal cancer. Methods: Medical records of 204 patients with de novo stage IV colorectal adenocarcinoma treated at Ankara Etlik City Hospital from December 2022 to December 2025 were reviewed retrospectively. Patients were grouped according to PTR status. Baseline clinicopathological features, molecular tumor profile, metastatic disease extent, treatment characteristics, and inflammatory-nutritional markers were recorded. Survival outcomes were assessed in terms of progression-free survival (PFS) and overall survival (OS) using the Kaplan–Meier method and Cox proportional hazards regression models, as well as 1:1 propensity score matching and sensitivity analyses. Results: PTR was performed in 114 patients (55.9%), while 90 patients (44.1%) did not undergo PTR. Patients who underwent PTR were younger, had better Eastern Cooperative Oncology Group (ECOG) performance status, and more frequently had single-organ metastatic disease. In the unmatched cohort, patients who underwent PTR had longer median PFS and OS than those without PTR (15.88 vs. 11.03 months and 16.14 vs. 11.54 months, respectively; both log-rank p < 0.001). In the adjusted Cox models, PTR corresponded to lower risks of progression (hazard ratio [HR]: 0.50; 95% confidence interval [CI]: 0.34–0.74; p < 0.001) and death (HR: 0.48; 95% CI: 0.30–0.77; p = 0.002), whereas BRAF mutation showed higher risks of progression (HR: 3.00; 95% CI: 1.70–5.29; p < 0.001) and death (HR: 3.42; 95% CI: 1.83–6.38; p < 0.001). In the propensity score–matched cohort comprising 50 matched pairs, PTR remained associated with a lower risk of progression or death (HR: 0.59; 95% CI: 0.40–0.87; p = 0.007), whereas its association with OS was not statistically significant (HR: 0.69; 95% CI: 0.42–1.13; p = 0.141). Sensitivity analyses generally yielded estimates favoring PTR, although the statistical significance of the association with OS varied across analyses. Patients with higher prognostic nutritional index (PNI) values showed more favorable survival outcomes. Conclusions: In this retrospective cohort, PTR was consistently associated with longer PFS, whereas its association with OS was less robust across the adjusted analyses. Because these patients had a more favorable baseline profile, these associations should be viewed with caution and in relation to patient selection. BRAF mutation and PNI emerged as important prognostic factors, supporting a multidimensional approach to survival assessment that incorporates metastatic disease burden, tumor biology, and inflammatory-nutritional status. Full article

Background/Objectives: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before 50 years of age, is increasing worldwide and may exhibit molecular features distinct from late-onset colorectal cancer (LOCRC). This study aimed to identify EOCRC-associated genes and evaluate the functional relevance of the leading candidate. Methods: Public transcriptomic datasets were used for age-stratified candidate-gene discovery and validation. Overall survival analysis prioritized candidates, followed by loss-of-function studies and pathway-focused analyses in colorectal cancer cell lines. Results: CEMIP, NKD2, and FOXQ1 were elevated in the EOCRC groups in the discovery and integrated validation analyses. Among them, only CEMIP was significantly associated with poorer overall survival. HCT116 and HT29 cells showed relatively high endogenous CEMIP expression, and CEMIP knockdown reduced relative viable cell biomass and migration in wound-healing and Transwell assays. CEMIP-associated transcripts were enriched in several pathways, including Hedgehog, Wnt/β-catenin, and TGF-β signaling. In TCGA colon adenocarcinoma samples, CEMIP correlated most strongly with PTCH1; however, the correlations with other Hedgehog components were weak or absent. CEMIP silencing decreased PTCH1 and GLI1 transcripts while increasing SMO, suggesting a coordinated but non-linear relationship. Conclusions: CEMIP is an EOCRC-associated candidate biomarker and a functional contributor to colorectal cancer cell viability and migration. Its relationship with PTCH1-related Hedgehog signaling is exploratory and warrants direct mechanistic validation. Full article