Search Results (1,030)

Background: Right-sided metastatic colon cancer represents a clinically distinct subgroup with inferior outcomes and uncertain optimal biologic treatment selection, even among patients with RAS wild-type disease. Real-world data focusing specifically on right-sided RAS wild-type metastatic colon cancer remain limited. This study aimed to describe clinicopathologic characteristics, metastatic patterns, treatment approaches, and survival outcomes in this population using a national multicenter registry. Methods: This retrospective multicenter cohort study was conducted using data from the ONKO-KOLON Türkiye registry. Patients with pathologically confirmed KRAS/NRAS wild-type metastatic colorectal cancer and available primary tumor localization were evaluated. The main analytic cohort included patients with right-sided metastatic colon cancer, defined as right colon or transverse colon tumors. Left-sided colon cancer patients were used as a contextual comparator, while rectal cancer patients were excluded from sidedness-based colon comparisons. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: Among 1079 patients in the source cohort, primary tumor localization was available in 1065 patients. Of these, 213 had right-sided colon cancer, 464 had left-sided colon cancer, and 388 had rectal cancer. In the right-sided cohort, median age was 61.5 years, 64.3% were male, and 66.7% had synchronous/de novo metastatic disease. Liver metastasis was the most common metastatic site (63.4%), followed by lymph node (31.0%), lung (21.1%), and peritoneal metastases (15.5%). First-line anti-VEGF-based treatment was used in 46.0% of patients, while anti-EGFR-based treatment was used in 40.8%. Among evaluable patients, the objective response rate was 46.8% and the disease control rate was 79.2%. Median progression-free survival was 10.0 months, and median overall survival was 24.0 months. In unadjusted exploratory analysis, median OS was 27.0 months with anti-EGFR-based treatment and 17.0 months with anti-VEGF-based treatment (log-rank p = 0.022), whereas median PFS was 10.0 months in both groups. In an extended covariate-adjusted multiple-imputation sensitivity model, the anti-EGFR OS estimate did not meet statistical significance (adjusted HR 0.66, 95% CI 0.43–1.00; p = 0.051). In a secondary contextual comparison, median overall survival was shorter in the right-sided than in the left-sided colon cancer group (24.0 vs. 28.0 months; HR 1.47, 95% CI 1.19–1.82; p < 0.001), whereas progression-free survival did not differ significantly. Conclusions: This study provides a descriptive account of metastatic patterns, treatment approaches, and outcomes in a dedicated right-sided RAS wild-type metastatic colon cancer cohort. The unadjusted OS difference between biological treatment groups was not confirmed after measured covariate adjustment and should not be interpreted as evidence of comparative treatment effectiveness. Because molecular profiling was incomplete, this study cannot identify biomarker-defined treatment subgroups. Prospective studies with complete, predefined molecular characterization are needed before molecularly informed treatment selection hypotheses can be evaluated in this population. Full article

Background: Head and neck cutaneous squamous cell carcinoma (HNcSCC) presents intersecting oncologic, functional, and reconstructive challenges. Although numerous clinicopathologic factors have been associated with recurrence, metastasis, and survival, their relationship with reconstructive complexity and patient-centered outcomes remains insufficiently studied. This review aimed to examine how established oncologic risk factors might inform reconstructive planning while distinguishing measured reconstructive evidence from hypothesis-generating clinical inferences. Methods: A structured PubMed/MEDLINE search conducted through 15 July 2026 was used to identify the literature addressing clinicopathologic prognostic factors in HNcSCC. Twenty-nine prognostic publications were retained for structured charting. Additional reconstructive, functional, aesthetic, and patient-reported outcome sources were identified through reference-list screening and were used solely for narrative contextualization. Because no dedicated multi-database systematic search of reconstructive outcomes was performed, the article is presented as a structured narrative review and hypothesis-generating research framework rather than a systematic review of reconstructive evidence. Results: The prognostic literature reported associations between adverse oncologic outcomes and factors including tumor size and depth, perineural invasion, lymphovascular invasion, poor differentiation, immunosuppression, recurrent disease, positive margins, nodal involvement, and extranodal extension. However, most of these studies did not measure post-excision defect characteristics, reconstructive technique, wound complications, functional recovery, scar quality, aesthetic outcomes, or patient-reported outcomes. Direct reconstructive evidence was limited and predominantly derived from site-specific, mixed-histology, technical, or methodological publications. Consequently, clinicopathologic factors should be regarded as potential upstream variables for future investigation rather than validated predictors of reconstructive outcomes. Conclusions: Current evidence supports oncologic risk stratification more strongly than prediction of reconstructive difficulty or patient-centered outcomes in HNcSCC. Prospective studies should jointly measure patient, tumor, treatment-field, defect, reconstructive, functional, aesthetic, and patient-reported variables. The proposed framework is intended to guide such research and is not a validated clinical prediction model. Full article

Alternative pre-mRNA splicing is a central layer of gene regulation that enables a limited number of genes to generate a far larger and more context-dependent transcriptome and proteome. In cancer, splicing is disrupted by mutations in cis-regulatory sequences, recurrent lesions in spliceosome components, altered abundance or activity of RNA-binding proteins, and changes in transcription, chromatin, RNA modification, metabolism and stress signalling. These alterations are not merely by-products of malignant transformation. They can create oncogenic protein isoforms, eliminate tumour-suppressive products, remodel cellular identity, promote metastasis and drug resistance, and generate tumour-restricted peptides that are visible to the immune system. Large pan-cancer datasets, long-read sequencing, single-cell isoform profiling, proteogenomics and functional perturbation screens are now resolving this complexity at unprecedented scale. In parallel, multiple therapeutic strategies are advancing, including modulators of the SF3B complex, molecular glues that degrade RBM39, inhibitors of protein arginine methyltransferases and splicing kinases, splice-switching oligonucleotides, programmable RNA-targeting systems, and vaccines or T-cell receptors directed against splicing-derived neoantigens. This review integrates the molecular logic of splice-site selection with the cancer-specific mechanisms that perturb it, summarizes representative isoform switches across the hallmarks of cancer, evaluates emerging technologies and clinical biomarkers, and discusses the opportunities and constraints of translating splicing biology into precision oncology. Particular emphasis is placed on tumour specificity, intratumoural heterogeneity, proteomic validation, therapeutic windows and rational combination strategies. Full article

Background/Objectives: Bone is the third most common site of solid-tumor metastasis, and surgical management spans a wide spectrum from observation to curative en bloc resection in selected patients. 18F-FDG PET/CT has been reported to alter oncologic management in 20% to 45% of patients across diverse settings, yet its specific impact on surgical decision-making within a multidisciplinary orthopedic oncology board (MOOB) reassessment and the predictors of decision change remain undefined. Methods: We retrospectively analyzed consecutive patients with histopathologically confirmed bone metastases evaluated at a tertiary-care MOOB between February 2023 and February 2026. For each patient, the surgical plan was recorded twice: first by the orthopedic team based on available conventional imaging (radiography, computed tomography, magnetic resonance imaging) and then as the final PET/CT-informed MOOB review. This design evaluates changes in decision-making intent after PET/CT-informed multidisciplinary reassessment, rather than the isolated causal effect of PET/CT or actual surgical implementation. Surgical plans were categorized as no surgery, palliative stabilization, palliative resection, or curative-intent resection, and changes were classified as no change, escalation, de-escalation, or cancellation. Results: Among 73 patients (mean age 64.7 ± 12.1 years; 53.4% male), the most frequent primaries were lung (37.0%), breast (21.9%), and renal cell carcinoma (13.7%). Following PET/CT-informed MOOB reassessment, the intended surgical plan changed in 53.4% of cases (p < 0.001), comprising surgery cancellation (27.4%), escalation (17.8%), and de-escalation (8.2%). Patients directed to no surgery increased fourfold (6.8% to 28.8%), and curative resection emerged as a post-reassessment recommendation (0% to 10.9%). SUVmax did not predict overall decision change, but higher SUVmax was associated with cancellation/de-escalation in the directional analysis. In exploratory multivariable analysis, polymetastatic disease (OR 0.051; 95% CI 0.005 to 0.547; p = 0.014), long-bone diaphyseal location (OR 0.133; p = 0.006), and higher Eastern Cooperative Oncology Group (ECOG) performance score (OR 2.109 per point; p = 0.018) independently predicted decision change. Conclusions: PET/CT-informed MOOB reassessment was associated with substantial changes in intended surgical strategy for metastatic bone disease. The findings support careful multidisciplinary integration of metabolic imaging, metastatic burden, anatomic location, and performance status, but should be regarded as hypothesis-generating until validated prospectively with data on treatment delivery and downstream outcomes. Full article

Cancer metastasis is the leading cause of cancer-related mortality, accounting for more than 90% of cancer deaths worldwide. However, the epigenetic mechanisms governing the metastatic cascade remain incompletely understood. Epigenetic reprogramming, including reversible changes in histone modifications, DNA methylation, chromatin remodeling, and non-coding RNA (ncRNA)-mediated regulation, enables tumor cells to acquire invasive, migratory, stem-like, and immune-evasive characteristics. During epithelial-to-mesenchymal transition (EMT), key epigenetic regulators such as histone deacetylases (HDACs), the Polycomb repressive complex 2 (PRC2) subunit EZH2, lysine-specific demethylase 1 (LSD1/KDM1A), and bromodomain and extraterminal (BET) proteins repress epithelial gene expression while activating mesenchymal transcriptional programs, promoting invasion and dissemination. At distant sites, epigenetic plasticity facilitates metastatic colonization through mesenchymal-to-epithelial transition (MET) and adaptive chromatin remodeling. Because these changes are reversible, they represent attractive therapeutic targets. HDAC, EZH2, LSD1/KDM1A, BET, and DNA methyltransferase (DNMT) inhibitors have shown promise in preclinical models of metastasis, with several advancing through clinical trials. Long non-coding RNAs, particularly HOTAIR, function as epigenetic scaffolds that reinforce metastatic programs, while reciprocal interactions between tumor cells and the tumor microenvironment (TME) drive epigenetic adaptations that promote immune evasion and metastatic progression. In addition, circulating tumor DNA (ctDNA) methylation signatures are emerging as minimally invasive biomarkers for assessing metastatic risk and monitoring treatment. This review summarizes current insights into the epigenetic regulation of cancer metastasis, evaluates emerging epigenetic therapies, and highlights translational opportunities to advance precision anti-metastatic strategies and improve patient outcomes. Full article

Background: HER2 is a key oncogenic gene in breast cancer, involved in tumor progression, metastasis, and therapeutic resistance. This study aimed to find new HER2 inhibitors using a hybrid of machine learning (ML) and structure-based virtual screening (VS), combined with molecular dynamics (MD) simulations on various scaffolds. Methods: Four supervised molecular fingerprint classification models were trained on a dataset of 10,000 validated compounds from ChEMBL. Random Forest was the top model for screening a large compound library. Selected compounds underwent molecular docking in the HER2 ATP binding site, ADMET, drug likeness, toxicity analysis, and 200 ns MD simulations. Methods like PCA, FEL, hydrogen-bond analysis, DCCM, RDF, salt-bridge analysis, and MM/PBSA were used to assess binding stability. Results: Virtual screening identified three compounds, CHMEBL193865 (Lead-1), CHMEBL46740 (Lead-2), and CHMEBL151318 (Lead-3)—with better binding affinity and interaction profiles than the reference inhibitor. MD simulations showed stable protein–ligand complexes with RMSD values of 2.32–2.76 Å. Among these, Lead-2 was the most structurally stable, and Lead-1 had the most favorable binding free energy. All three compounds showed good drug likeness, ADMET properties, and low predicted toxicity. Conclusions: These findings support further in vitro and in vivo testing for developing new therapeutics against HER2-overexpressing breast cancer, highlighting two scaffolds with promising lead optimization potential. Full article

Background/Objectives: Improved preoperative prediction of nodal metastasis in prostate cancer could refine selection for extended pelvic lymph node dissection, a high-morbidity procedure. Sperm-associated antigen 1 (SPAG1) is a candidate marker of nodal status, but its incremental value beyond clinical staging and the associated transcriptional state remain unevaluated. Methods: In The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) cohort (497 patients with matched clinical and RNA-sequencing data), we evaluated the association between SPAG1 expression and pathological N stage by logistic regression with 2000-resample bootstrap optimism correction and sensitivity analyses for missing nodal data and batch effects. Hallmark enrichment analysis compared SPAG1 expression extremes (quartile 4 vs. 1) and, separately, N1 versus N0 tumours adjusted for T stage, Gleason grade, and tissue source site; directional concordance was assessed. Results: N1 rates rose across SPAG1 quartiles from 7.6% to 39.0% (per-quartile odds ratio [OR], 1.83; p = 2.55 × 10⁻⁵). After adjusting for T stage and Gleason grade, SPAG1 remained an independent predictor (adjusted OR, 2.14; 95% confidence interval [CI], 1.50–3.13; p = 4.8 × 10⁻⁵), stable across both sensitivity analyses. Adding SPAG1 improved discrimination (area under the receiver-operating characteristic curve, 0.783 to 0.838; ΔAUC, 0.056; paired DeLong p = 3.03 × 10⁻⁵). The SPAG1 transcriptional programme showed cell-cycle, immune–inflammatory, and mTORC1/TGF-β signalling activation with suppressed differentiation and metabolism; all 15 overlapping Hallmark pathways were directionally concordant with the adjusted N1 signature. Conclusions: SPAG1 expression in primary prostate tumours is a candidate predictor of pathological lymph node metastasis with statistically robust incremental discrimination beyond clinical staging. Independent external validation and biopsy-based feasibility studies are required before clinical application. Full article

Background: Cetuximab-based therapies continue to play an important role in the management of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) despite the increasing use of immunotherapy. However, data regarding treatment outcomes and prognostic factors remain limited. This study aimed to evaluate treatment outcomes and prognostic factors associated with survival in patients with R/M HNSCC treated with cetuximab-based regimens. Methods: This retrospective single-center cohort study included patients with recurrent/metastatic HNSCC who received cetuximab-based systemic therapy at the Department of Medical Oncology, Manisa Celal Bayar University Faculty of Medicine, between May 2012 and September 2025. Demographic, clinical, laboratory, and PET/CT data were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with survival were evaluated using univariable and multivariable Cox proportional hazards regression analyses. Results: A total of 57 patients were included in the study. The median age was 65 years, and 91.2% of patients were male. Most patients had ECOG performance status 0–1 (94.7%) and stage IV disease (71.9%). The larynx was the most common primary tumor site (50.9%), while distant lymph node metastasis (63.2%) and lung metastasis (61.4%) were the predominant metastatic sites. Median PFS and OS were 4.6 months and 13.8 months, respectively. Kaplan–Meier analysis demonstrated that patients with a body mass index (BMI) > 25 had longer OS, whereas chronic kidney disease (CKD), primary tumor localization, and best response to first-line treatment were significantly associated with survival. In multivariable Cox regression analysis, chronic kidney disease (CKD) (HR: 5.15, p = 0.004), oral cavity primary tumor localization (HR: 2.55, p = 0.013), progressive disease as the best response to first-line treatment (HR: 4.44, p < 0.001) and the absence of grade 1–2 cetuximab-related dermatologic toxicity (HR: 3.20, p = 0.027) remained independent adverse prognostic factors. BMI was not independently associated with survival in multivariable analysis. Conclusions: Cetuximab-based therapy demonstrated clinically meaningful activity in patients with R/M HNSCC. Comorbidities, primary tumor localization, the absence of grade 1–2 cetuximab-related dermatologic toxicity and treatment response appear to substantially influence survival outcomes. Larger prospective studies are warranted to validate these findings. Full article

Immune checkpoint inhibitors (ICIs) are now being introduced into perioperative treatment for several solid tumors. This strategy is usually explained by tumor reduction before surgery or by the elimination of minimal residual disease (MRD) after surgery. However, these explanations may not be sufficient to understand why the timing of ICI treatment, especially before lymph node (LN) removal, is important. In this review, we discuss tumor-draining lymph nodes (tdLNs) from two different aspects. tdLNs are anatomical routes for regional and distant metastasis, but they are also sites where tumor antigens are presented and tumor-specific T cell responses are generated. In particular, preclinical and translational studies suggest that tdLNs may maintain stem-like or progenitor-exhausted T cells (TPEX) that can respond to PD-1 blockade and supply more differentiated exhausted T cells to tumor sites. However, current clinical trials of perioperative ICIs demonstrate therapeutic benefit in specific diseases and regimens, but do not directly establish tdLN preservation or tdLN-resident TPEX maintenance as the decisive mechanism of efficacy. We therefore present the tdLN-reservoir model as a hypothesis-generating framework rather than as a clinically validated basis for modifying lymph node management. We also discuss the possible roles of neoadjuvant and adjuvant ICI in relation to antigen flow, minimal residual disease, metastatic-site draining LNs, postoperative lymphatic dysfunction, and future immune-guided clinical trials. Importantly, current evidence does not support altering standard lymph node surgery or radiotherapy solely to preserve putative tdLN immune-reservoir function. Full article

Background: Soft tissue sarcomas (STS) in children, adolescents, and young adults are rare and biologically heterogeneous, and prognostic factors for local recurrence, metastasis, and survival remain incompletely defined. This study aimed to characterize oncological outcomes and to explore clinical, surgical, and treatment-related factors associated with these endpoints at a tertiary sarcoma center. Methods: This retrospective single-center cohort study included 42 consecutive patients aged ≤25 years with histologically confirmed STS who underwent definitive surgery between June 2018 and November 2025. Local recurrence-free (LRFS), metastasis-free (MFS), event-free (EFS), and overall survival (OS) were estimated by the Kaplan–Meier method with competing-risks sensitivity analyses. Given the limited number of events, pre-specified univariable comparisons (log-rank, Fisher exact, Mann–Whitney U) were performed and regarded as exploratory. Results: The median age was 16.7 years and 26 patients (61.9%) were female. A microscopically complete (R0) resection was achieved in 35 of 41 patients with assessable margins (85.4%), and limb preservation in 38 (90.5%). Over a median follow-up of 23.1 months, the 24- and 60-month estimates were LRFS 85.7% and 79.6%, MFS 93.3% and 84.8%, EFS 82.3% and 64.7%, and OS 96.0% and 81.5%, respectively. Metastatic disease at diagnosis was the only variable associated with metastatic status at last follow-up (p = 0.035). No factor was robustly associated with local recurrence; anatomical site (p = 0.68), resection-margin status (p = 0.23), and tumor volume (p = 0.97) were not significant, and an apparent association with a sub-millimeter margin rested on a single event (complete separation). Conclusions: Metastatic disease at diagnosis emerged as the most important prognostic factor for MFS in our cohort. Despite the complexity of treatment in this young patient population, high rates of complete resection and limb preservation were achieved, highlighting the value of multidisciplinary management in specialized sarcoma centers. While the limited cohort size did not allow the identification of further statistically significant prognostic factors for local recurrence, such associations may become detectable in larger multicenter studies. Full article

Background/Objectives: Thymidylate synthase (TYMS) represents an important therapeutic target. Methods: In this study, TYMS expression was analyzed by immunohistochemistry on a tissue microarray containing 17,371 samples from 136 different tumor types. Results: TYMS staining was seen in 42.9% of 15,361 analyzable tumors, with weak staining in 35.4%, moderate in 5.7%, and strong in 1.8%. TYMS occurred in at least one case of 127 categories, of which 71 showed TYMS staining in at least 50% of cases, and 56 included at least one case with strong positivity. TYMS positivity occurred most commonly in lymphomas (81.3–96.5%), sarcomas and sarcomatoid carcinomas (33.3–100%), malignant melanoma (70.5–90.7%), cervical adenocarcinoma (78.3%), and squamous cell carcinomas of various sites (57.1–77.9%). High TYMS expression was linked to advanced pT (p = 0.0097), high grade (p < 0.0001), ER negativity (p < 0.0001), and PR negativity (p = 0.0002) in invasive breast cancer of no special type; high grade (p < 0.0050), high UICC stage (p = 0.0060), and nodal metastasis (p = 0.0120) in clear cell renal cell carcinoma (RCC); high grade (p < 0.05) and nodal metastasis (p = 0.0045) in papillary RCC; high Gleason grade (p < 0.0001) and advanced pT stage (p = 0.0149) in prostatic adenocarcinoma; high pT (p < 0.0001), nodal metastasis (p = 0.005), lymphatic (p = 0.0064) and venous invasion (p = 0.0005), left side location (p < 0.0001), and microsatellite instability (p < 0.0001) in colorectal adenocarcinoma; and high grade (p < 0.0001) in squamous cell carcinomas of different sites. Conclusions: TYMS is often overexpressed across different cancer entities and shows associations with several adverse histopathological parameters commonly used to describe tumor phenotypes. Full article

Cancer remains a major global health challenge and is the second leading cause of death worldwide. Targeted therapy has emerged as one of the most promising strategies for cancer treatment. However, current targeted therapies highlight the urgent need for novel therapeutic targets and strategies. The provirus integration site for Moloney murine leukemia virus 1 (PIM1) kinase has been identified as a key factor in tumor progression and poor prognosis. This review systematically summarizes and analyzes the diverse mechanisms of PIM1 in promoting tumor progression, including cell programmed death, cell cycle progression, DNA damage response, metastasis, cell stemness, metabolic reprogramming, tumor angiogenesis, anti-cancer immune response and therapeutic resistance, and comprehensively evaluates its potential as a therapeutic target. Moreover, PIM1 contributes to the development of resistance to various anticancer therapies. Based on the advances and limitations in PIM1-targeted cancer therapy, we propose that future research should focus on combination strategies involving PIM1 inhibitors and agents targeting parallel or upstream/downstream pathways regulated by PIM1. Our review highlights the therapeutic value and potential of PIM1 in cancer treatment, providing new insights and theoretical bases for the development of novel anti-tumor strategies targeting PIM1. Full article

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, highlighting the need for safer and more effective chemopreventive strategies. Although many phytochemicals can modulate key molecular processes involved in breast carcinogenesis, their chemopreventive potential largely depends on delivery strategies that preserve their biological activity and enable efficient accumulation at the target site. Protein-based nanocarriers have emerged as promising delivery systems capable of improving the protection, solubility, cellular uptake, targeted delivery, and controlled release of bioactive compounds in tumor tissues. This review summarizes recent advances in selected animal- and plant-derived protein nanocarriers used for the encapsulation and delivery of natural compounds in breast cancer chemoprevention. Particular attention is given to their physicochemical properties, encapsulation performance, release behavior, biological activity, targeting potential, and translational limitations. Furthermore, the mechanisms underlying the enhanced anticancer activity of encapsulated phytochemicals, including improved stability, receptor-mediated uptake, pH-responsive release, apoptosis induction, oxidative stress modulation, and inhibition of tumor growth and metastasis, are highlighted. Current challenges, including enzymatic degradation, formulation instability, immunogenicity concerns, manufacturing scalability, and limited clinical evidence, remain important barriers to translation. Overall, selected protein-based nanocarriers represent promising multifunctional platforms for improving the chemopreventive potential of natural compounds in breast cancer. Full article

Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform. Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis. Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal–chemotherapeutic effect in 4T1 TNBC cells. Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo. Full article

Background: Head and neck neuroendocrine carcinoma (HN-NEC) is exceedingly rare. Standardized treatment strategies for this malignancy remain unestablished. This study aimed to explore promising treatment modalities, and to identify prognostic factors in HN-NEC. Materials and Methods: Thirty-nine patients diagnosed with HN-NEC at West China Hospital of Sichuan University between 2006 and 2025 were enrolled. The 5-year survival rates were estimated by Kaplan–Meier analysis. The log-rank test and Firth’s penalized Cox multivariable analysis regression model were used to identify prognostic factors. Results: The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates for patients who did and did not receive radiotherapy were 63.2% vs. 29.6% (p = 0.031), 75.5% vs. 48.0% (p = 0.065), and 81.4% vs. 46.9% (p = 0.039), respectively. Laryngeal NEC was associated with poorer 5-year DMFS (41.2% vs. 87.5%, p = 0.023) and 5-year OS (38.1% vs. 92.9%, p = 0.027) compared with non-laryngeal HN-NEC. Radiotherapy (HR = 0.152, 95% CI: 0.025–0.757, p = 0.022) was a potentially protective factor influencing LRRFS. Conclusions: Radiotherapy may be associated with improved LRRFS in patients with HN-NEC. HN-NEC originating in the larynx appeared to be associated with a poorer prognosis compared with other primary sites of the head and neck. Full article