Search Results (1,375)

Background: Precision oncology has significantly transformed the management of non-small cell lung cancer (NSCLC) through the integration of molecular diagnostics, targeted therapies, and biomarker-driven treatment selection. Advances in next-generation sequencing (NGS) and liquid biopsy have improved the identification of actionable molecular alterations and enabled dynamic monitoring of tumor evolution. Objective: To provide a structured narrative review of current evidence regarding actionable molecular biomarkers, diagnostic methodologies, targeted therapies, and future directions in NSCLC precision oncology, with a specific focus on conceptualizing acquired resistance mechanisms. Methods: A structured narrative literature review was conducted by searching PubMed and Google Scholar for English-language studies published between 2015 and 2026. Eligible publications included clinical trials, cohort studies, translational research, reviews, and clinical guidelines addressing molecular profiling, targeted treatments, diagnostic approaches, and resistance mechanisms in NSCLC. Results: A total of 99 foundational studies and clinical documents were analyzed. Key actionable biomarkers included EGFR (Epidermal Growth Factor Receptor), ALK (Anaplastic Lymphoma Kinase), ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase), KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog), RET (Rearranged during Transfection), MET (Mesenchymal–Epithelial Transition Factor), HER2 (Human Epidermal Growth Factor Receptor 2) and NTRK (Neurotrophic Tyrosine Receptor Kinase) alterations, along with emerging targets such as NRG1 (Neuregulin 1) fusions. NGS emerged as the cornerstone of comprehensive molecular profiling, while liquid biopsy enabled longitudinal monitoring of tumor dynamics and resistance development. To organize the biological complexity of treatment failure, acquired resistance mechanisms were categorized into a three-tiered conceptual framework: target-centric genetic evolution (Tier 1), cellular plasticity and intratumoral heterogeneity (Tier 2), and non-genetic/microenvironmental adaptation (Tier 3). Targeted therapies significantly improved clinical outcomes compared with conventional chemotherapy; however, acquired resistance remained a major challenge across all tiers. Conclusions: Precision oncology in NSCLC is evolving from a biomarker-focused approach toward a dynamic framework integrating molecular diagnostics, targeted therapies, and continuous resistance monitoring. The proposed three-tiered resistance framework provides a structured basis for understanding treatment failure, guiding molecular reassessment at progression, and informing future adaptive therapeutic strategies to improve long-term patient outcomes. Full article

The Alternative Lengthening of Telomeres (ALT) pathway drives replicative immortality in aggressive malignancies, particularly sarcomas and gliomas. Clinical ALT stratification has relied on screening for structural ATRX and DAXX mutations. However, this genotypic approach fails to capture the dynamic macro-reprogramming required to sustain ALT. Here, we established and validated a 28-gene transcriptomic signature that captures the ALT-associated transcriptomic phenotype of the ALT phenotype. Using multivariate Cox proportional hazards models and time-dependent ROC analyses, we demonstrate that this signature is a robust, independent predictor of poor overall survival in Sarcoma (SARC) and Lower Grade Glioma (LGG) cohorts, outperforming the prognostic value of traditional ATRX/DAXX mutational status. Genomic mapping revealed this transcriptional synchrony is structurally facilitated by non-random focal clustering on Chromosome 8. To deconstruct the machinery driving this lethal phenotype, we employed an integromic approach, synthesizing protein–protein and metabolic flux networks. Topological algorithms prioritized five indispensable hubs: TP53, ATM, ATR, PCNA, and UBE2I. Gene–metabolite profiling identified PCNA as a bottleneck funneling extreme deoxyribonucleotide (dNTP) demand to sustain break-induced telomeric recombination. To translate these vulnerabilities into actionable treatments, we mapped these hubs to a precision pharmacological network. We propose a multi-targeted strategy combining FDA-approved PARP inhibitors to exploit ATR-mediated synthetic lethality, alongside antimetabolites to induce nucleotide starvation. This study redefines ALT risk stratification and provides a data-driven framework to target and treat resistant ALT-positive tumors. Full article

Intraosseous arteriovenous malformations (AVMs) of the mandible are rare but potentially life-threatening vascular anomalies in childhood. We report the case of a 7-year-old girl with an initially misdiagnosed (“keratocystic”) lesion who presented with recurrent intraoral bleeding, swelling, and tooth loosening of the right mandible. Magnetic resonance and angiographic imaging revealed an extensive intraosseous mandibular AVM extending into the peri-mandibular soft tissues, with arteriovenous shunts and a venous aneurysm. Following emergency hemostasis and blood transfusion, a total of five staged interventional radiological embolization procedures were performed between 2023 and 2024. Acute bleeding episodes could be controlled; however, sustained remission was not achieved. During the course of treatment, the patient developed a submandibular abscess and post-traumatic stress disorder (PTSD). Histopathological examination demonstrated a vascular malformation without evidence of malignancy. Molecular genetic testing identified a somatic KRAS (Kirsten rat sarcoma virus) mutation. Due to insufficient response to interventional therapy, systemic treatment with the MEK (mitogen-activated protein kinase) inhibitor trametinib was initiated to facilitate future surgical resection. Under this therapy, marked clinical and radiological improvement was observed with good tolerability. This case (3-year observation period) highlights the diagnostic risk of misinterpreting an osteolytic lesion, the importance of early diagnosis, the interdisciplinary staged and combined approach, the potential of molecular targeted therapy with an MEK inhibitor in treatment-refractory pediatric mandibular AVMs, and the continued relevance of surgical treatment strategies. These findings should be interpreted with appropriate caution and require validation in prospective studies. Full article

Background/Objectives: Evidence regarding associations between local therapy before an indexed systemic regimen and subsequent outcomes in advanced soft tissue sarcoma (STS) remains limited. We evaluated outcomes within four regimen-defined cohorts and explored associations with prior local-therapy history. Methods: This retrospective cohort included 75 patients with recurrent or metastatic STS who contributed 155 treatment episodes: doxorubicin (n = 44), trabectedin (n = 31), pazopanib (n = 42), and eribulin (n = 38). Progression-free survival (PFS) and overall survival (OS) were measured from initiation of the indexed regimen. Surgery, local ablative therapy, and radiation therapy were assessed separately and in combined categories. Post hoc analyses were restricted to leiomyosarcoma. Results: Median PFS was 3.4, 3.1, 5.1, and 3.9 months, respectively. PFS was longer with any local therapy and surgery and/or ablation in the trabectedin cohort (p = 0.0342 and p = 0.0111) and with surgery and/or ablation in the eribulin cohort (p = 0.0352). Longer indexed-regimen OS was observed in surgery-containing categories in the doxorubicin and eribulin cohorts. In selected multivariable models, local therapy was associated with OS in doxorubicin- and eribulin-treated episodes and with PFS in eribulin-treated episodes. Leiomyosarcoma-restricted analyses did not consistently reproduce the full-cohort findings. Conclusions: Prior local-therapy history was associated with PFS or OS in selected within-cohort analyses. The associations may reflect local-treatment effects, differences among selected patients, or both; however, the study cannot distinguish these contributions. No between-regimen differences were formally tested. These findings support individualized multidisciplinary assessment and external validation. Full article

Background/Objectives: Rare histologic subtypes of cervical cancer are uncommon and may be misclassified during initial diagnosis. Their recognition depends on subtype-directed immunohistochemistry, which excludes metastatic mimics, and on high-risk HPV (hrHPV) testing, which establishes HPV status. Published series rarely report how the diagnosis was reached. We therefore documented the full diagnostic work-up, together with treatment and outcomes, in a consecutive single-center series. Methods: This was a retrospective, single-center case series (January 2020–January 2025). Rare tumors were defined per the 2020 WHO Classification as subtypes other than squamous cell carcinoma and usual-type adenocarcinoma. Immunohistochemistry was used to confirm lineage and exclude mimics. hrHPV DNA testing and p16 immunohistochemistry were performed where tissue permitted. A tumor was called HPV-associated only when diffuse block-type p16 positivity accompanied hrHPV DNA; HPV DNA alone was not accepted as evidence of an HPV-driven tumor. Results: Ten patients were included (median age 53 years). There were two signet-ring cell adenocarcinomas, two small cell neuroendocrine carcinomas (SCNECC), two serous adenocarcinomas, and one each of sarcomatoid carcinoma, clear cell carcinoma, granulocytic sarcoma, and poorly differentiated adenosquamous (glassy cell) carcinoma. hrHPV DNA was detected in six of the seven tumors tested. Three of these six were p16-negative: one serous, the clear cell, and the glassy cell carcinoma. Because diffuse block-type p16 expression is a validated surrogate marker of transcriptionally active hrHPV, we classified these three as HPV-independent. This matches the known biology of these histotypes. Lymphovascular space invasion was present in eight patients (80%). Over a median follow-up of 10.5 months, four patients developed distant metastases and three died. Conclusions: Accurate diagnosis of rare cervical tumors requires subtype-directed immunohistochemistry to exclude mimics and hrHPV testing interpreted together with p16; HPV DNA positivity alone does not establish HPV-association. Given the small, heterogeneous series, outcome data are descriptive and hypothesis-generating. We propose a diagnostic algorithm and immunohistochemical framework and advocate centralized review and prospective registries. Full article

Purpose: This review aims to provide an updated overview of Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in colorectal carcinoma (CRC), focusing on their role in tumorigenesis, prognostic implications, and recent advances in targeted therapy. Major findings: KRAS mutations occur in approximately 40% of colorectal cancers and play a central role in tumour initiation and progression through constitutive activation of MAPK pathways. Clinically, KRAS mutations are well established as predictors of resistance to anti-EGFR therapy. Increasing evidence also supports their role as prognostic biomarkers, with KRAS-mutant tumours associated with increased recurrence risk and reduced survival, including in patients undergoing hepatic metastasectomy. Therapeutically, recent advances, most notably KRAS G12C inhibitors and combination strategies targeting upstream or parallel pathways, have expanded treatment options, although efficacy varies across KRAS mutation subtypes. Conclusions: KRAS mutations have important implications for the behaviour, prognosis, and management of colorectal cancer. Integrating KRAS mutational status into clinical decision-making may enable more personalised prognostication and treatment strategies. Continued research is required to broaden effective targeted therapies for the diverse spectrum of KRAS-mutant disease. Full article

Background/Objectives: Pediatric solid tumors (PST) are a biologically distinct group of malignancies whose developmental origins and molecular drivers differ substantially from those of adult cancers, with direct implications for therapeutic strategy and clinical outcome. This review synthesizes current evidence on molecular pathogenesis, tumor microenvironment biology, and the structural conditions that shape access to care across select PST. Methods: A narrative review of peer-reviewed literature was conducted primarily using PubMed, supplemented by Google Scholar, covering publications from 2000 to 2025. Tumor types were selected based on their prevalence in the pediatric population and the availability of evidence addressing both molecular features and health disparities. Body: Across eight tumor types (neuroblastoma, Ewing sarcoma, pediatric brain tumors, rhabdomyosarcoma, Wilms tumor, retinoblastoma, osteosarcoma, and chondrosarcoma), recurrent molecular alterations including MYCN amplification, EWS-FLI1 fusions, PAX-FOXO1 rearrangements and IDH 1/2 mutations emerge as central determinants of disease behavior and eligibility for treatment. The tumor microenvironment manifests as a shared mediator of immune exclusion and therapeutic resistance across tumor types, with, but not limited to, tumor-associated macrophages, myeloid-derived suppressor cells, and checkpoint molecule expression, identified as recurrent features influencing treatment response. Immunotherapeutic strategies have shown variable efficacy across PST, with the most consistent clinical benefit established in neuroblastoma. A critical and underappreciated pattern stands out across tumor types: children carrying the most aggressive molecular subtypes are disproportionately those with the least access to therapies those subtypes demand, emphasizing an overlap of biological and structural disadvantage that is also amplified in low- and middle-income countries, where late-stage presentation, treatment abandonment and limited access to molecular diagnostics compound the biological disadvantage. Conclusions: Within the eight PST reviewed, the most aggressive molecular subtypes and the greatest structural disadvantages converge in the same children; those carrying MYCN amplification, PAX-FOXO1 fusions, or EWS-FLI1 fusions are disproportionately those with the least access to the therapies their biology demands. Genomic and immunologic advances will only reach their full clinical potential when paired with inclusive trial data, diversified genomic databases, and most importantly, equitable access to biomarker-specialized therapies across all populations. Full article

This review summarises current evidence on renal cell carcinoma (RCC) with sarcomatoid dedifferentiation (sRCC), with an emphasis on diagnosis, prognostic stratification, and treatment. Sarcomatoid dedifferentiation is characterised by high-grade spindle cell morphology, occurs in 2–26% of all RCC patients, predominantly in the clear cell subtype (~70%), and is WHO/ISUP grade 4 regardless of extent of involvement. Thus, sRCC represents a pathological transformation rather than a distinct entity. Diagnosis requires biopsy or nephrectomy; immunohistochemical (IHC) retention of PAX8, cytokeratins, and vimentin alongside loss of subtype-specific markers distinguishes sRCC from primary renal sarcoma. On CT, sRCC typically presents as a large, heterogeneous mass with extensive necrosis; 18F-FDG PET/CT carries independent prognostic value, though no feature is pathognomonic. Sarcomatoid features are approximately five times more prevalent in patients with metastatic vs. localised disease (~20 vs. ~4%), and their identification should prompt risk stratification. Median overall survival (OS) in metastatic sRCC is 5.9–13.3 months, though recent data suggest improvement with novel therapies. Sarcomatoid dedifferentiation is characterised by enrichment of alterations in TP53, BAP1, CDKN2A/B, and NF2 on a background of founder RCC mutations, generating an immune-inflamed tumour microenvironment with elevated CD8+ T cell infiltration and PD-L1 expression that may underpin the heightened sensitivity of sRCC to immune checkpoint inhibitors (ICI). Surgery remains the cornerstone in localised disease, although recurrence rates approach 80% within two years. Adjuvant pembrolizumab significantly improved disease-free survival in high-risk localised RCC with sarcomatoid features (KEYNOTE-564; NCT03142334). In the metastatic setting, nivolumab plus ipilimumab and pembrolizumab plus axitinib are preferred first-line regimens. Full article

Epithelioid sarcoma (EPS) is an ultra-rare malignant mesenchymal neoplasm of uncertain differentiation that comprises two distinct clinicopathological subtypes: classic and proximal. Classic EPS most commonly occurs in the distal upper extremity of adolescents and young adults, whereas proximal-type EPS most often affects the truncal regions of young to middle-aged adults. Both classic and proximal-type EPSs exhibit aggressive clinical behavior, including a higher risk of local recurrence and regional lymph node or distant metastasis. Histologically, classic EPS is characterized by irregular nodules composed of epithelioid and spindled cells, while proximal-type EPS consists of multinodular distributions and sheets of large polygonal cells. EPS has a distinctive immunoprofile with characteristic expression of cytokeratins and epithelial membrane antigen. Loss of nuclear expression of SMARCB1 protein occurs in the vast majority of cases. Moreover, SMARCB1 homozygous deletions have also been observed in both subtypes. Surgery is the mainstay treatment approach for localized EPS. Systemic treatment options for metastatic or unresectable locally advanced disease are very limited. The withdrawal of tazemetostat has created a significant gap in available treatment options. In this review, we provide an overview of the current knowledge on the clinical and radiological features, histopathology, immunohistochemistry, pathogenesis, and management of EPS. Full article

Diffusion-weighted imaging (DWI) has evolved from a niche research sequence into an increasingly valuable adjunct to conventional magnetic resonance imaging (MRI) in musculoskeletal (MSK) radiology. By providing qualitative and quantitative information on tissue microstructure through assessment of water diffusion and apparent diffusion coefficient (ADC) mapping, DWI offers functional insights beyond conventional morphological imaging. We aim to present the current evidence for DWI in MSK imaging organised around established applications and emerging applications, with particular emphasis on composition-related interpretive pitfalls relevant to differentiating tumours and other pathologies, and to review the technique’s evolving role in routine practice. This narrative review synthesises the current literature on the clinical utility of DWI in MSK imaging. It is structured in four parts: foundations and the tissue composition signal framework, including the basis of qualitative and quantitative assessment; established applications; emerging applications; and assessment of tissue composition-related interpretive as well as technical pitfalls, including those arising due to myxoid matrix, chondroid matrix, blood degradation products, organising thrombus, crystalline or mineralised material, keratinaceous debris, purulent content, cellular haematopoietic marrow, by using original cases from the authors’ institution, which have been confirmed either histologically or surgically. Applications are stratified by strength of evidence. Established applications of DWI include soft tissue abscess detection, differentiation of malignant from benign soft tissue tumours, differentiation of malignant from benign vertebral compression fractures, and myeloma staging and response assessment, as well as treatment response in soft tissue and bone sarcomas. Whole-body MRI with DWI for staging and response assessment in multiple myeloma is guideline-endorsed and supported by prospective multicentre data. Soft tissue abscess detection, soft tissue and bone tumour characterisation, and characterisation of vertebral compression fractures are supported by consistent evidence from multiple independent cohorts, although no universally transferable ADC threshold exists. The emerging applications, which are promising adjuncts supported by small, single-centre or heterogeneous studies with thresholds that have not been externally validated, include ADC ghost sign in osteomyelitis (high specificity but sensitivity of only 20%), peripheral nerve sheath tumour characterisation and surveillance in NF1 patients, peripheral neuropathy and plexopathy, predisposing conditions such as Li Fraumeni syndrome in paediatric cancers, inflammatory myopathy, and postsurgical assessment of residual disease, as well as opportunistic detection of venous thrombosis. Radiomics and machine learning approaches remain experimental. Recent technical advances, including reduced field-of-view imaging, multi-shot acquisition and improved fat suppression, have mitigated but not eliminated historical limitations of susceptibility artefacts and limited spatial resolution. DWI has become an important functional imaging technique that complements conventional MRI across a broad range of musculoskeletal disorders. Understanding the relationship between tissue composition and the diffusion signal is central to both interpreting DWI correctly and avoiding its characteristic pitfalls. DWI is best regarded not as a stand-alone technique but as one component of a multiparametric assessment, in which its functional information is integrated with conventional morphological imaging. Ongoing technical improvement and expanding clinical evidence are expected to further support its integration into routine MSK imaging and its development as a quantitative biomarker for diagnosis, prognostication, and treatment monitoring. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies due to limited responsiveness to chemotherapy and the high prevalence of oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Co-delivery of cytotoxic agents and small interfering RNA (siRNA) is a potential combination strategy, but the two cargos have distinct physicochemical and intracellular-delivery requirements. Here, we developed a chitosan–polyethylene glycol (CP)-based polymeric nanoparticle platform for the cotreatment of paclitaxel (PTX) and small interfering RNA (siRNA) targeting KRAS G12D mutation. PTX was first modified to PTX-COOH through an ester-containing succinate linker and then covalently conjugated to the polymer backbone through amide bond formation, enabling stable nanoparticle formation and subsequent electrostatic complexation with siRNA. The CP-PTX-siRNA nanoparticles demonstrated efficient cellular uptake, while luciferase knockdown by CP-siRNA supported functional siRNA delivery by the CP carrier. In KRAS G12D–mutant pancreatic cancer cells, PTX- and KRAS-targeting siRNA-coloaded nanoparticles resulted in enhanced cytotoxicity compared to single-agent treatments and free drug combinations, with combination index values below 1 indicating calculated synergy under the tested in vitro conditions. Because KRAS knockdown and a non-targeting siRNA control were not assessed in PANC-1 cells, the enhanced cytotoxicity cannot be attributed specifically to KRAS silencing. Across multiple drug-to-siRNA ratios, nanoparticle formulations consistently improved treatment potency. Together, these results support CP-PTX-siRNA nanoparticles as a modular and biocompatible platform for combined PTX/siRNA delivery. This approach provides a versatile strategy for combining chemotherapeutic agents with RNA-based therapeutics in PDAC, supporting further development of these polymeric nanocarriers for combination cancer therapy. Full article

Background/Objectives: Survival in children, adolescents and young adults (CAYA) with bone sarcoma remains inferior to that of many other early-life cancers. Early recognition and treatment initiation may reduce the risk of presenting with advanced disease. We aimed to synthesize evidence on five predefined diagnostic intervals, separately synthesize pathway-specific intervals, and identify factors associated with diagnostic interval duration. Methods: A systematic review was conducted according to PRISMA guidelines. We included studies reporting the duration of a diagnostic interval in at least five patients aged 0–39 years with primary bone sarcomas, including osteosarcoma, Ewing sarcoma, and less common histological subtypes. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus were searched for studies published between 2000 and 2025. Risk of bias was assessed using a custom domain-based tool. Results: Twenty-nine studies including 9271 patients from high-income countries met the inclusion criteria. Substantial heterogeneity in study design, populations, and interval reporting precluded meta-analysis. Reported median intervals were patient intervals of 13–84 days, diagnostic intervals of 15–123 days, total diagnostic intervals of 28–150 days, treatment intervals of 7–24 days, and total intervals of 66–88 days. Older age within the CAYA population and axial tumor location were the factors most consistently associated with longer diagnostic intervals. No consistent association between diagnostic interval duration and survival was identified. Pathway-specific intervals provided additional insight into different components of the diagnostic pathway, particularly after initial healthcare contact, although evidence remained limited. Conclusions: Diagnostic interval durations varied substantially across studies, reflecting methodological heterogeneity and differences in diagnostic pathways. Standardized prospective studies are needed to strengthen the evidence base. Full article

Kaposi’s Sarcoma Herpesvirus (KSHV) is the etiological agent of Kaposi’s Sarcoma (KS), which induces metabolic stress in infected host cells. KSHV reprograms host metabolic pathways for efficient viral replication and infectious virion production. Here, we report a time-course global metabolomics study conducted in iSLK.BAC16 cells to compare latent and lytic KSHV infection. Our data show that amino acid, central carbon, and nucleotide metabolic pathways are highly dysregulated upon reactivation. During lytic KSHV infection, pathway enrichment analysis identifies purine and pyrimidine metabolism as the top two most significantly impacted and dysregulated pathways. Further experiments have shown that nucleotide metabolism is required during lytic KSHV infection to produce maximal infectious virus. Treatment with the FDA-approved drug, methotrexate (MTX), a folate antagonist that decreases nucleotide metabolism by reducing tetrahydrofolate cofactors, significantly reduced KSHV copy number and late lytic viral gene expression upon reactivation compared to controls. Additionally, titers of cell-free supernatants from MTX-treated lytic samples showed a significant reduction in infectious virion production. Furthermore, MTX significantly decreased the viral titer of murine herpesvirus 68 (MHV-68), a model virus to study gammaherpesvirus. Overall, our study demonstrates that metabolic inhibition during lytic gammaherpesvirus infection decreases productive infection and hence serves as a potential therapeutic antiviral target. Full article

Kaposi’s Sarcoma Herpesvirus (KSHV), an enveloped double-stranded DNA virus, is the etiological agent of Kaposi’s Sarcoma (KS), an endothelial cell-based tumor. KSHV is a leading cause of infection-related cancers in sub-Saharan Africa and immunocompromised individuals worldwide. Therefore, it is vital to identify the underlying mechanisms of viral infection and transmission to effectively identify specific therapeutic strategies and combat the disease. Here, we demonstrate that KSHV rewires the host cell lipidome during lytic infection. Bulk lipidomic analysis shows significant changes in the abundance of neutral lipids and phospholipids during lytic infection. We further investigated fatty acid binding proteins (FABPs) to understand the underlying mechanisms that support KSHV pathogenesis. Using the doxycycline-inducible iSLK.BAC16 cell line, we find that FABP genes are differentially regulated by lytic KSHV infection compared to latent infection. We report that FABP4 is significantly upregulated during lytic infection. FABP4 knockdown using siRNA or inhibition of the FABP4 protein via treatment with a competitive inhibitor during lytic infection significantly reduces extracellular viral titers, indicating that FABP4 supports maximal infectious virion production. This study highlights the role of FABP4 as a host target that facilitates KSHV infection and pathogenesis. 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