Search Results (2,016)

Background/Objectives: Image-guided adaptive brachytherapy is a core component of definitive treatment for locally advanced cervical cancer (LACC). However, implantation remains challenging in bulky, asymmetric, or anatomically complex tumors, where standard applicator geometry or purely straight interstitial trajectories may be insufficient for individualized target coverage. This study evaluated the real-world implementation of a patient-specific 3D-printed template-guided adaptive brachytherapy workflow for complex LACC. Methods: We retrospectively reviewed 120 consecutive patients with FIGO 2018 stage IB3–IVA cervical cancer treated with definitive chemoradiotherapy followed by high-dose-rate image-guided brachytherapy between March 2023 and March 2025. All patients were treated using a patient-specific 3D-printed template-guided hybrid intracavitary/interstitial workflow integrating CT/MRI-based target assessment, individualized catheter trajectory planning, template fabrication, implantation verification, and adaptive treatment planning. Straight-channel or curved-channel guidance was selected according to residual tumor geometry and pelvic anatomy, with flexible plastic interstitial catheters used for curved or anatomically constrained trajectories. Procedural deliverability, dosimetry, toxicity, early clinical outcomes, and exploratory dose–outcome patterns were analyzed. Results: The median HR-CTV volume was 55.9 cm³, and the median HR-CTV D90 was 92.9 Gy EQD2. Median organ-at-risk D2cc values remained within contemporary institutional and guideline-consistent constraints. A total of 555 template-guided HDR brachytherapy fractions were delivered. The median applicator-and-catheter placement time was 4.21 min per fraction, with a median of 7.25 implanted channels. Minor and major insertion-related bleeding occurred in 10.8% and 1.7% of patients, respectively. At a median follow-up of 20.1 months, estimated 3-year overall survival, progression-free survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were 77.9%, 76.8%, 94.3%, 98.0%, and 86.2%, respectively. Late grade ≥ 3 gastrointestinal and genitourinary toxicities occurred in 2.5% and 1.7% of patients, respectively, with no grade 4–5 events. Exploratory dose–outcome analyses suggested hypothesis-generating dose–outcome patterns, but these findings were not intended to define or validate a clinical dose threshold. Conclusions: This real-world implementation study supports the feasibility of patient-specific 3D-printed template-guided adaptive brachytherapy for complex LACC. By translating CT/MRI-based individualized trajectory planning into template-guided intracavitary/interstitial catheter placement, this workflow achieved guideline-consistent target coverage, acceptable organ-at-risk doses, efficient procedural delivery, and low severe toxicity within the available follow-up. Dose–outcome findings remain exploratory and require validation in more mature cohorts. Full article

Background and Objectives: Breast cancer is the leading oncological diagnosis among women in Kazakhstan, yet a substantial proportion of cases are still detected beyond the earliest stages, particularly in peripheral regions such as Aktobe. Despite a national mammography screening programme covering women aged 40–70 years since 2018, structural differences in access to early diagnosis—related to geography, socioeconomic circumstances, and the diagnostic pathway—may compromise outcomes. We aimed to identify factors independently associated with early-stage presentation and to characterise the temporal pattern of early-stage presentation without assuming a monotonic trend. Methods and Materials: We conducted a retrospective, population-based analytical study of all confirmed breast cancer cases (ICD-10 C50) registered in the Aktobe regional cancer registry and diagnosed between 1 January 2015 and 31 December 2025 (n = 2232). The outcome was early-stage presentation, defined literally as Stages I–IIa at diagnosis, with Stages IIb–IV as the comparator; this is a stage-at-presentation classification and is not intended to indicate surgical operability or treatment sequence. Multivariable logistic regression estimated adjusted odds ratios (aORs). Two models were used: Model A included age, sex, residence, administrative nationality, employment/social status, and calendar year; Model B additionally included the diagnostic pathway, which may lie on the causal pathway between structural determinants and stage. Calendar year was modelled as a categorical variable, and a complementary phase-based model (2015–2017, 2018–2019, 2020–2022, 2023–2025) was fitted. A residence-by-year interaction; a multinomial sensitivity analysis separating Stages IIb, III, and IV; discrimination (AUC, Brier score); and calibration (Hosmer–Lemeshow test, calibration plot) were also assessed. Results: Of 2232 patients (99.1% female; mean age 57.0 ± 12.5 years), 1323 (59.3%) presented at Stages I–IIa. In Model A, rural residence (aOR 0.77, 95% CI 0.64–0.93; p = 0.006), unemployment relative to employment (aOR 0.69, 95% CI 0.52–0.90; p = 0.007), Russian administrative nationality (aOR 0.64, 95% CI 0.50–0.82; p < 0.001), and other non-Kazakh nationalities (aOR 0.73, 95% CI 0.58–0.94; p = 0.012) were independently associated with lower odds of Stage I–IIa presentation. In Model B, patient-initiated (self-referral) presentation was associated with lower odds relative to clinical examination room detection (aOR 0.46, 95% CI 0.30–0.72; p < 0.001), whereas organised screening was not significantly associated (aOR 1.52, 95% CI 0.95–2.43; p = 0.082). The calendar-year pattern was clearly non-linear (categorical vs. linear year: likelihood-ratio χ² = 76.1, df = 9, p < 0.001): odds of Stage I–IIa presentation peaked in 2018 (aOR 2.49, 95% CI 1.57–3.93 vs. 2015), were lowest in 2022 (aOR 0.64, 95% CI 0.42–0.97), and partially recovered thereafter. In the phase-based model (reference 2015–2017), the aORs were 1.62 (95% CI 1.22–2.15) for 2018–2019, 0.54 (95% CI 0.41–0.69) for 2020–2022, and 0.62 (95% CI 0.46–0.84) for 2023–2025. Model discrimination was limited (AUC 0.648, 95% CI 0.625–0.671; Brier score 0.226) with acceptable calibration (Hosmer–Lemeshow χ² = 8.38, df = 8, p = 0.40). Conclusions: In this registry-based cohort, rural residence, unemployment, non-Kazakh administrative nationality, and patient-initiated presentation were independently associated with lower odds of early-stage breast cancer presentation. The temporal pattern was non-monotonic, with the highest odds around the 2018 screening expansion, a marked reduction during 2020–2022, and only partial recovery thereafter. These are observational associations rather than causal or programme-evaluation findings; they should be interpreted as hypothesis-generating and require confirmation with screening-process, service-capacity, and patient-level access data. Full article

Radiotherapy is a cornerstone of breast cancer treatment, but its efficacy is frequently limited by intrinsic and acquired radioresistance as well as dose-limiting toxicity to surrounding normal tissues. Nanoparticle-mediated radiosensitization has emerged as a promising strategy to enhance the therapeutic index of irradiation by combining physical dose amplification with biological, microenvironmental, and immunological modulation. In this systematic review, we evaluated preclinical evidence on nanoparticle-mediated radiosensitization in breast cancer, with emphasis on nanoplatform design, mechanistic patterns, therapeutic efficacy, and translational relevance. A total of 66 studies published between 2015 and 2026 were included. The identified systems encompassed a broad range of materials, including gold-, silver-, platinum-, bismuth-, gadolinium-, polymer-, lipid-, and hybrid-based nanoplatforms, frequently incorporating targeting ligands, catalytic components, biomimetic coatings, or therapeutic payloads. Enhanced radiation responses were most commonly associated with high-atomic-number (high-Z)-mediated energy deposition, increased reactive oxygen species generation, and enhanced DNA damage persistence. Additional mechanisms, including redox modulation, hypoxia targeting, regulated cell death, and immune activation, reflect the evolution of nanoparticle-assisted radiotherapy from predominantly physical radioenhancement toward multifunctional physicobiological strategies. Triple-negative breast cancer models predominated throughout the literature. Across preclinical models, nanoparticle-assisted irradiation consistently improved clonogenic survival, tumor control, and, in selected studies, survival. However, substantial heterogeneity in study design and limited use of rigorous radiobiological endpoints restricted cross-study comparability. The available preclinical evidence indicates that the most promising nanoparticle-mediated radiosensitization strategies integrate physical dose enhancement with biologically active mechanisms targeting oxidative stress, hypoxia, persistent DNA damage, immune signaling, and tumor microenvironmental resistance. Collectively, these findings suggest that the field is evolving from predominantly physical radioenhancement toward multifunctional, mechanism-driven physicobiological strategies. However, clinical translation remains constrained by methodological heterogeneity and limited radiobiological validation, highlighting the need for standardized preclinical evaluation and clinically feasible nanoplatforms tailored to subtype-specific mechanisms of radioresistance. Full article

Background: Patient-derived functional models have emerged as promising translational platforms capable of reproducing tumour-specific treatment sensitivity patterns, which could be used to personalise neoadjuvant treatment for patients with rectal cancer. Herein, we aimed to summarise the current comparative evidence in a meta-analytical framework on radiotherapy response between preclinical platforms and matched patient data. Methods: A systematic review was performed according to PRISMA principles to identify studies evaluating patient-derived functional models for the prediction of radiotherapy or chemoradiotherapy response in rectal cancer. Study characteristics, experimental protocols, predictive performance and clinical correlations were extracted. An exploratory hierarchical summary receiver operating characteristic (HSROC) meta-analysis was performed using studies providing sufficient data. Results: Eight studies involving patient-derived organoids and zebrafish patient-derived xenograft models were included. Most studies evaluated locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. The included studies demonstrated concordance rates ranging from 78% to 100% between ex vivo functional responses and matched clinical treatment outcomes. Reported predictive performance was favourable, with Yao et al. demonstrating 85.0% concordance, 78.0% sensitivity and 92.0% specificity, while Hsu et al. reported 87.5% sensitivity and 100% specificity using radiobiological modelling. Exploratory HSROC analysis demonstrated overall favourable discriminatory performance for prediction of treatment resistance and poor response. Conclusions: Patient-derived functional models, particularly PDOs, demonstrate promising potential as predictive biomarkers for radiotherapy and chemoradiotherapy response in rectal cancer. Although the current evidence remains exploratory and is limited by methodological heterogeneity and small cohorts, these platforms represent a promising translational strategy in precision radiation oncology, warranting prospective multicentre validation. Full article

Respiratory medicine is transitioning from symptom-driven, standardized care to a more precise, patient-specific approach guided by molecular profiling. This evolution is being enabled by advances in liquid biopsy, multiomics, and artificial intelligence (AI) analytics. Fractional exhaled nitric oxide (FeNO) and blood eosinophils, the two commonly used markers in asthma, are now being joined by more precise airway markers such as galectin-10, which could aid clinicians in making more informed decisions for biological treatments. In chronic obstructive pulmonary disease (COPD) similar progress is underway, with treatment now emphasizing inflammation endotypes, especially eosinophilic patterns, to direct therapeutic choices. Alongside these developments, routine blood-based ratios (e.g., platelet-to-lymphocyte and neutrophil-to-lymphocyte) are being explored as predictors of exacerbation risk, and forced oscillation testing (FOT) is proving useful for picking up early disease shifts. In more severe conditions, biomarkers are linked to an early and better prognosis, enabling timely intervention. Markers like Matrix metalloproteinase-7 (MMP-7) and CC chemokine ligand 18 (CCL18) have proven to be reliable indicators of mortality and disease progression in idiopathic pulmonary fibrosis. Meanwhile, in lung cancer, liquid biopsies, especially those measuring circulating tumor DNA and micro-RNA (miRNA) panels, are enhancing screening accuracy while helping to cut down on the high false-positive rates seen with low-dose computerised tomography (CT). Other respiratory conditions such as bronchiectasis, pulmonary embolism, pneumonia, and acute respiratory distress syndrome (ARDS) are also benefiting from biomarker advances. At the same time there is a growing push to standardize how these biomarkers are measured. AI-based clinical decision support systems are also playing an increasingly important role in the translation of all these complicated data into actionable clinical insights. Together these developments pave the way for improved respiratory care that is precise and responsive to individual patient needs. Full article

Renal cell carcinoma (RCC) is frequently resistant to tyrosine kinase inhibitors (TKIs) such as sunitinib, limiting therapeutic efficacy. ATP-binding cassette (ABC) transporters, including ABCB1, ABCB5, and ABCG2, are important transporters implicated in multidrug resistance, influencing drug efflux and tumor progression. We aimed to evaluate the expression of ABCB1, ABCB5, and ABCG2 in human RCC tissues and human renal cancer cell lines CAKI-2 and A-498, and to investigate their potential association with sunitinib resistance and associated signaling pathways. Twenty paired tumorous and adjacent non-tumorous human kidney tissue samples were analyzed for ABC transporter gene expression using qRT-PCR. RCC cell lines CAKI-2 and A-498, including sunitinib-resistant derivatives, were treated with 40 µM sunitinib. The levels of transporters and key signaling proteins were assessed by Western blot. ABCG2 was consistently higher in tumorous tissues, and ABCB1 and ABCB5 showed grade-dependent increases in tumors. Resistant cells exhibited elevated ABCB1 and dynamic ABCB5 and ABCG2 expression patterns compared to sensitive cells, indicating an association between altered transporter expression and the resistant phenotype. Sunitinib treatment modulated signaling pathways, with differential activation of PI3K/Akt, NF-κB, and MAPK/ERK observed in sensitive versus resistant cells. Our findings suggest that altered ABCB1 and ABCG2 expression may be associated with the development of sunitinib resistance in RCC and may be linked to changes in key survival signaling pathways. These findings provide a basis for future functional studies investigating the role of ABC transporters in sunitinib resistance and may contribute to the development of personalized therapeutic strategies in RCC. Full article

Background: Cancer-related psychological distress is a major concern in comprehensive oncology care because it substantially impairs patients’ quality of life and may adversely affect treatment adherence, outcomes, and prognosis. Over the past decade, research in this field has expanded rapidly; however, the overall knowledge structure, global research patterns, major contributors, and emerging hotspots remain insufficiently characterized. A bibliometric analysis is therefore needed to systematically map the development of cancer-related psychological distress research and identify evolving directions for future investigation. Methods: Publications related to cancer-related psychological distress published between 1 January 2015 and 31 December 2024 were retrieved from the Web of Science Core Collection and Scopus databases. The database searches were conducted on 10 March 2025. Bibliometric analyses were performed using VOSviewer (version 1.6.20), CiteSpace (version 6.3.R1), and the R package bibliometrix (version 5.3). Publication trends, country and institutional contributions, journal distribution, author collaboration networks, co-cited references, keyword co-occurrence, burst keywords, and thematic evolution were analyzed. Results: A total of 7063 publications were included in the bibliometric analysis, including 6162 articles and 901 reviews. Annual publication output increased from 465 publications in 2015 to 924 publications in 2024. The main contributing countries were the United States, Australia, China, Germany, and the United Kingdom. The United States ranked first in publication volume and total citations. Psycho-Oncology and Supportive Care in Cancer were the leading journals by publication volume and total citations. Major research themes included quality of life, psychological distress, depression, anxiety, breast cancer, distress screening, survivorship, and palliative care. Seven high-frequency keywords—“cancer,” “quality of life,” “psychological distress,” “depression,” “anxiety,” “breast cancer,” and “distress”—each appeared more than 500 times, representing the core research topics. Emerging keywords such as “informal caregivers,” “young adults,” “guidelines,” and “adult survivors” reflected increasing attention to caregiver support, age-specific psychosocial needs, survivorship care, and standardized clinical management. Conclusions: This bibliometric analysis provides a comprehensive overview of global research on cancer-related psychological distress from 2015 to 2024. The findings reveal publication trends, major contributors, collaboration patterns, core research themes, knowledge structures, and emerging topics in this field. Current research has gradually shifted from general descriptions of psychological distress toward survivorship care, caregiver support, standardized screening, and guideline-based management. Future studies should strengthen interdisciplinary collaboration, improve standardized assessment and screening approaches, and further explore emerging areas such as caregiver support, young adult cancer populations, survivorship care, and digital health and artificial intelligence-assisted approaches, which require further validation before routine clinical implementation. Full article

Background: Left ventricular (LV) dysfunction is a clinically important complication of anthracycline- and trastuzumab-based treatment in breast cancer. Inflammatory pathways may contribute to cancer therapy-related cardiac dysfunction, and the CD40/CD40 ligand (CD40L) axis has been implicated in vascular inflammation and myocardial injury. This study assessed longitudinal changes in CD40 and CD40L during adjuvant treatment and their association with LV dysfunction. Methods: Twenty-eight women with operable breast cancer receiving adjuvant anthracycline-based chemotherapy with or without trastuzumab were prospectively evaluated. Blood samples were collected at baseline, 6 months, and treatment completion at 15 months to measure CD40 and CD40L. Cardiac function was assessed by transthoracic echocardiography, including left ventricular ejection fraction and global longitudinal strain, at baseline and every 3 months. Repeated-measures analysis of variance examined temporal biomarker changes and interactions with LV dysfunction. Results: Participants had a mean age of 52.6 ± 10.7 years and a mean BMI of 25.8 ± 4.8 kg/m²; 64% were postmenopausal, 76% had HER2-positive disease, and 79.3% received radiotherapy and trastuzumab. During follow-up, 15 patients (53.6%) developed LV dysfunction. CD40 levels remained stable overall (p = 0.31), whereas CD40L increased significantly over time (p < 0.001). Baseline CD40 did not differ by LV dysfunction status (p = 0.79). However, CD40 showed a significant time-by-LV dysfunction interaction (p = 0.022), increasing late in patients with LV dysfunction and declining in those without it. CD40L showed no such interaction (p = 0.85). Conclusions: In this small exploratory cohort, CD40 demonstrated differential longitudinal patterns according to subsequent LV dysfunction, whereas CD40L increased over time without a clear association with LV dysfunction. These findings should be interpreted as hypothesis-generating and require validation in larger prospective cohorts. Full article

The present study investigates the pro- and anti-apoptotic responses of HepG2 liver cancer cells to Ornithogalum sigmoideum (O. sigmoideum) and Smilax excelsa (S. excelsa) extracts, aiming to identify their potential as anti-cancer agents. Methanolic extracts of O. sigmoideum and S. excelsa were prepared, and their phytochemical profiles were analyzed by Gas Chromatography–Mass Spectrometry (GC-MS). Cytotoxicity and IC50 values were determined in HepG2 cells using the MTT assay. The relative mRNA expression of apoptotic genes (BAX, BCL-2, and Caspase-3) was quantified by qPCR, and the treatment effect size was calculated using Cohen’s d. GC-MS analysis revealed distinct phytochemical profiles; S. excelsa was rich in phenolic compounds, while fatty acid esters and alcohols dominated Ornithogalum extracts. O. sigmoideum bulb extract exhibited the strongest cytotoxicity (IC50 = 125.57 µg/mL), followed by the leaves (IC50 = 156.43 µg/mL), whereas Smilax showed minimal toxicity (IC50 = 304.15 µg/mL). Mechanistically, the O. sigmoideum leaf extract showed gene expression patterns consistent with pro-apoptotic signaling, including upregulation of BAX and Caspase-3 mRNA. O. sigmoideum extracts, especially from leaf parts, exhibit significant cytotoxicity, and the transcriptomic profile is consistent with apoptotic pathway activation in HepG2 cells, positioning it as a candidate for further mechanistic investigation. Full article

Cancer predisposition syndromes (CPSs) account for 8.5–18% of all childhood cancer cases. Most of them are inherited in an autosomal dominant pattern; consequently, there is a 50% risk of transmission to offspring. Early detection of CPSs is crucial for choosing patient treatment strategies and for counseling in the family. This study enrolled 886 pediatric patients with hematologic and solid neoplasms from prospective and retrospective cohorts (2018–2025). Clinical exome or multigene panel sequencing was used to analyze blood DNA. Overall, 186 pathogenic/likely pathogenic (PLP) variants in cancer-associated genes were identified in 176/886 (20%) of patients, and the most frequently mutated were the NF1 (n = 35) and TP53 (n = 18) genes. Among the 186 PLP variants, 126/886 (14.2%) were causative for pediatric neoplasms, while 56/886 (6.3%) were heterozygous mutations associated with adult-onset CPSs affecting DNA repair. The highest total mutation rate was revealed in retinoblastoma (80%), peripheral nerve sheath tumors (60%), and pheochromocytoma/paraganglioma (47%), while the lowest rate was found in hematologic malignancies (4.6%) and neuroblastoma (12%). The wide range and high frequency of deleterious variants in pediatric patients, especially in those with solid tumors, highlights the importance of multigene panel sequencing for the accurate determination of CPSs. Full article

Background/Objectives: Psychosocial, neuropsychological, social, and academic difficulties may persist after pediatric cancer treatment. We described parent/caregiver-reported functioning and support needs and explored their associations with clinical, family-related, socio-economic, premorbid, and place-based characteristics in an Italian survivorship setting. Methods: This single-center cross-sectional exploratory study included 93 of 130 families approached between November 2022 and January 2023 (response rate, 71.5%). One parent or caregiver completed a purpose-built questionnaire for each survivor. The cohort included 38 survivors with central nervous system (CNS) tumors and 55 with non-CNS tumors. Outcomes were evaluated relative to retrospectively reported pre-diagnosis functioning. Exact confidence intervals, effect estimates, multivariable Firth logistic regression, and Benjamini–Hochberg false discovery rate correction were used. Results: Worsening internalizing difficulties were reported for 48/90 survivors (53.3%), neuropsychological difficulties for 42/90 (46.7%), academic worsening for 30/85 (35.3%), and social integration difficulties for 27/90 (30.0%). CNS survivors more frequently had social integration difficulties than non-CNS survivors (47.4% versus 17.3%; odds ratio, 4.22; 95% confidence interval, 1.50–12.73; q = 0.015) and underwent cognitive assessment after cancer (50.0% versus 17.0%; odds ratio, 4.80; 95% confidence interval, 1.71–14.44; q = 0.013). Municipality size and geographic area showed no nominal associations with parent-reported outcomes. No candidate-variable association in the exploratory screen remained significant after false discovery rate correction. Conclusions: Parent-reported difficulties and support needs were common, with differences by CNS versus non-CNS tumor site. Family-related, premorbid, and place-based patterns are hypothesis-generating and require prospective evaluation using validated multi-informant measures. Full article

Background: Rheumatoid arthritis (RA) is linked to increased risks of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), malignancy, and mortality. However, differences in these risks by treatment class—particularly among older adults with cardiovascular (CVD) risk factors—remain unclear. Methods: We conducted a population-based cohort study using Ontario administrative data. Patients aged ≥67 years with incident RA (2008–2013) were followed through 2023. Outcomes included healthcare utilization for MACE and VTE, all-cause mortality, and cancer-related encounters. Time-varying treatment groups were: no csDMARD/advanced therapy (AT), glucocorticoids (GC) only, csDMARDs (reference), and biologic/targeted synthetic DMARDs (b/tsDMARDs). Weighted Fine–Gray models within a marginal structural framework were used, stratified by baseline CVD risk. Results: Among 10,058 patients, 80% had high CVD risk. Compared with csDMARDs, untreated patients (SHR 15.0; 95% CI 13.8–16.2) and GC users (SHR 1.29; 95% CI 1.13–1.47) had higher MACE risk, while AT use was associated with lower risk (SHR 0.53; 95% CI 0.37–0.77). Similar patterns were observed in low-risk patients. AT use was not associated with VTE. Untreated and GC users had increased mortality, whereas AT use reduced mortality. Increased cancer-related utilization was observed only in untreated patients. Conclusion: Treatment type strongly influences major outcomes in older adults with RA, underscoring the importance of integrating CVD and thrombotic risk into therapeutic decisions. Full article

Background: The cellular heterogeneity and spatial organization patterns of the tumor microenvironment (TME) play a crucial role in colorectal cancer (CRC) progression, but their spatial distribution and cellular communication mechanisms require further elucidation. This study aims to systematically dissect the cellular heterogeneity and spatial organization characteristics of the CRC microenvironment by integrating single-cell and spatial transcriptomic data. Methods: Single-cell RNA sequencing and spatial transcriptomics data of primary CRC were integrated to characterize the TME. Intercellular signaling patterns were elucidated through communication analysis, spatial niche clustering, ligand–receptor pair analysis, and spatial expression mapping. The ESTIMATE algorithm was applied to assess the correlation between TME scores and pathway-associated genes. Drug sensitivity prediction was performed using the oncoPredict. Results: Single-cell analysis identifies nine major cell types, revealing significant cellular heterogeneity. Intercellular communication analysis demonstrates that the MIF signaling pathway plays a prominent role within the TME communication network, with MIF-(CD74+CD44) and MIF-(CD74+CXCR4) identified as dominant receptor complexes. Spatial transcriptomic analysis reveals distinct spatial functional partitioning of these signaling axes. Signaling flow analysis indicates an immunosuppressive “tumor–immune” axis mediated by MIF signaling from tumor epithelial cells to immune cells. MIF expression is negatively correlated with ImmuneScore, while its receptors CD74, CD44, and CXCR4 are positively correlated. Drug sensitivity analysis reveals potential associations between key genes (MIF, CD74, CD44, and CXCR4) in the MIF pathway and various anti-tumor drugs. Conclusions: Our study reveals the cellular heterogeneity of the CRC microenvironment from multiple perspectives, elucidates the key mechanisms of the MIF signaling pathway, and provides potential therapeutic targets for CRC treatment. Full article

Cancer development arises from dynamic interactions between inherited susceptibility and modifiable environmental exposures, among which diet plays a central role. Carotenoids, lipophilic plant-derived pigments including lycopene, α-carotene, and β-carotene, and retinoids, the vitamin A derivatives that regulate gene transcription via retinoic acid receptors (RARs) and retinoid X receptors (RXRs), have been extensively investigated for their chemopreventive and therapeutic potential. This review aims to provide an integrated, mechanism-based synthesis of the roles of lycopene, α- and β-carotene, and retinoids in cancer chemoprevention and to clarify the conditions under which they are most likely to be effective. Beyond summarizing established antioxidant and nuclear-receptor mechanisms, we highlight as a novel emphasis the epigenetic actions of these compounds, including effects on DNA methylation, histone modification, and microRNA regulation, and we integrate these with the well-recognized divergence between dietary and high-dose supplement outcomes. Experimental evidence demonstrates that carotenoids modulate oxidative stress, inflammation, proliferation, apoptosis, angiogenesis, and metastasis through pathways such as Nrf2/ARE, NF-κB, STAT3, Akt/mTOR, MAPK, and Wnt/β-catenin. Lycopene, in particular, exhibits strong antioxidant capacity and multi-target signaling effects, while provitamin A carotenoids additionally influence retinoid-mediated transcriptional programs. Retinoids exert broader differentiation-inducing and antiproliferative effects through direct nuclear receptor signaling and represent one of the few successful differentiation therapies in oncology, most notably in acute promyelocytic leukemia. Epidemiologic studies generally associate higher dietary carotenoid intake with reduced risk of several malignancies, including prostate, breast, lung, colorectal, and gastric cancers. However, randomized trials of isolated high-dose supplementation, particularly β-carotene in smokers, have demonstrated null or harmful effects, highlighting a critical divergence between whole-food dietary patterns and pharmacologic supplementation. In conclusion, carotenoids and retinoids possess biologically plausible anticancer properties, yet their clinical utility remains context dependent. Future research should prioritize biomarker-guided, precision-based strategies, standardized formulations, and whole-food dietary approaches to clarify their role in cancer prevention and treatment. Full article

The treatment landscape of oncogene-driven non-small-cell lung cancer (NSCLC) has evolved substantially with the development of targeted therapies directed against actionable molecular alterations. Tyrosine kinase inhibitors (TKIs) remain the cornerstone of treatment for many driver-defined subsets; however, acquired resistance, central nervous system progression, and tumor heterogeneity continue to limit long-term disease control. This review examines the mechanistic foundations, clinical evidence, resistance patterns, and emerging therapeutic roles of TKIs, antibody–drug conjugates (ADCs), and bispecific antibodies (bsAbs) in oncogene-driven NSCLC. Relevant preclinical studies, clinical trials, and recent therapeutic advances across major actionable driver alterations were reviewed and compared. TKIs provide potent and selective inhibition of oncogenic signaling and remain the preferred frontline therapy in most molecular subgroups, whereas ADCs offer targeted payload delivery that may overcome diverse resistance mechanisms, and bsAbs provide dual-target blockade and immune-mediated antitumor activity. Emerging evidence supports the expanding role of ADCs and bsAbs in post-TKI settings and selected biomarker-defined populations. Resistance mechanisms differ across therapeutic classes and include secondary target alterations, bypass pathway activation, antigen loss, payload resistance, and receptor adaptation. Collectively, these modalities are increasingly being integrated into biomarker-guided treatment strategies, with future management likely to rely on rational sequencing and combination approaches tailored to resistance mechanisms, target expression, central nervous system involvement, and tumor heterogeneity. Full article