BACKGROUND:Thyroid nodule ultrasound (US) images and their features are of great importance in thyroid nodule diagnosis and can be helpful for radiologists' clinical decision making. The aim was to evaluate whether an artificial intelligence (AI)-assisted system can accurately characterize thyroid nodule US features and assist radiologists in diagnosing thyroid cancer. METHODS:The AI-assisted system (MDT-TC) was trained and internally validated on B-mode US images from 7204 lesions in 6884 patients in Southwest Hospital. The model performance was validated using 3 independent external validation cohorts. RESULTS:Echogenicity (ECH) and shape (SHA) are features of high importance for model recognition, and these features lead to excellent model performance. The model achieved up to 87.56% accuracy in determining ECH attributes and 69.21% in identifying shape categories. The area under the receiver operating characteristic curve (AUC) of the internal validation cohort and 3 independent external validation cohorts for MDT-TC were 0.951, 0.837, 0.816, and 0.871, respectively. The sensitivity values were 98.7%, 91.2%, 90.3%, and 85.6%, respectively. The AUC for the accurate diagnosis of radiologists with MDT-TC assistance was significantly higher than that of radiologists without MDT-TC assistance (P < .001). In addition, the AUC for the accurate diagnosis of junior doctors with MDT-TC assistance was significantly higher than that for those without (P < .01). CONCLUSION:MDT-TC incorporates radiomic features extracted from thyroid lesion US images and can significantly improve the diagnostic performance of radiologists. This result was particularly strong for junior doctors. Therefore, our data support the idea that MDT-TC can help to identify patients with thyroid cancer and could greatly benefit clinical practice.

The activation of endoplasmic reticulum stress (ERS), specifically the PERK/eIF2α/CHOP signaling, is a recognized consequence of ischemic stroke. However, the roles and mechanisms of CRM-1 regulating ERS in stroke are poorly elucidated. A murine model of stroke was generated via transient middle cerebral artery occlusion (MCAO). The endpoints included TTC-derived infarct volume, H&E/TUNEL histopathology, p-PERK immunohistochemistry, and Western blot. Oxygen-glucose deprivation/reoxygenation (OGD/R) was employed in HT22 neurons. The CRM1-ALKBH5 interaction and subcellular distribution were assessed by co-immunoprecipitation (co-IP), cytoplasm-nucleus fractionation, and confocal microscopy. m6A regulation of BANF1 was examined using MeRIP-qPCR, RIP-qPCR, and a dual-luciferase reporter assay. Knockdown of CRM-1 reduced the infarct size, decreased ER stress activation, decreased apoptosis in vivo, and improved cell viability after OGD/R. CRM-1 was attached to ALKBH5 and promoted its export from the nucleus, which increased m6A modification and expression on BANF1. IGF2BP2 and YTHDF1, respectively, enhanced the stability and translation of BANF1 mRNA, thereby upregulating its expression. BANF1 overexpression restored PERK/eIF2α/CHOP activation and apoptosis in the CRM-1 knockdown context. CRM-1 exacerbated ischemic stroke injury by exporting ALKBH5 to upregulate BANF1 in an m6A-IGF2BP2/YTHDF1-dependent manner. This cascade subsequently activated the PERK/eIF2α/CHOP ERS pathway.

Early detection of cancers initially misdiagnosed as benign (false-negative imaging diagnoses) remains a critical challenge in clinical practice. While artificial intelligence (AI) and deep learning have shown promise in analyzing medical imaging data with high efficiency and precision, existing models are often limited by their cancer-type specificity and dependence on specific imaging protocols. This lack of generalizability hinders their clinical utility for identifying missed malignancies in lesions previously classified as benign. We developed ENhanced Feature Identifies Early Cancers (ENFIEC), a deep learning system designed to detect malignancies in lesions originally diagnosed as benign via imaging. We evaluated ENFIEC's performance across three distinct datasets-breast, thyroid, and lung lesions-to assess its validity and generalizability in correcting false-negative diagnoses. The areas under the curve (AUC) of cancer detection in these datasets were 0.948, 0.972, and 0.880, respectively. ENFIEC outperformed the state-of-the-art deep learning methods by up to 18.6 %, showing its ability to address in samples from diverse types of lesions, and provided a generalizable foundation for early cancer detection. Furthermore, compared with results derived from radiologists, ENFIEC showed better prediction accuracy of early cancers (sensitivity, 96.5 % versus 69.3 %, P < 0.0001), enhancing junior radiologists' prediction accuracy of early cancers (88.0 % versus 55.7 %, P <0.0001) across three datasets. ENFIEC provides a generalizable solution for identifying false-negative cancer diagnoses in lesions initially classified as benign via ultrasound or CT. By improving detection accuracy, it has strong potential to reduce diagnostic errors and enhance early cancer detection in clinical practice.

e12668 Background: For patients with early-stage HER2-positive breast cancer, neoadjuvant therapy represents a cornerstone of modern management. The combination of trastuzumab and pertuzumab (HP) alongside chemotherapy constitutes the current evidence-based standard. Emerging evidence indicates that an alternative dual blockade strategy pairing trastuzumab with pyrotinib (HPy) also demonstrates promising efficacy with a manageable toxicity profile. In routine clinical practice, the selection between these two potent targeted regimens (HP versus HPy) remains a critical and unresolved decision point, necessitating further comparative evaluation. Methods: This prospective, multicenter, observational real-world study enrolled patients with stage II-III HER2-positive breast cancer. Treatment allocation to either the HP or HPy group was based on physician recommendation and patient preference. The administered chemotherapeutic backbones included: 6 cycles of TCbHP/TCbHPy, 4 cycles of EC followed by 4 cycles of THP/THPy, or 6 cycles of THP/THPy. The primary study endpoint was the total pathological complete response (tpCR) rate, defined as ypT0/is ypN0. Statistical analyses incorporated propensity score matching (PSM) to mitigate baseline imbalances. Results: Between January 2022 and June 2025, 687 patients from 10 participating hospitals were enrolled. As of the current analysis, 520 patients have completed neoadjuvant therapy and subsequent surgery with evaluable data, comprising 320 in the HP cohort and 200 in the HPy cohort. Initial comparisons revealed significant differences in chemotherapy regimens and Ki-67 expression levels between the groups. To address potential selection bias, a 1:1 PSM was performed, yielding 382 well-matched patients (191 per group) with balanced baseline characteristics. Prior to matching, the tpCR rates were 61.25% for the HP group and 53.00% for the HPy group, a difference that was not statistically significant ( P = 0.064). After PSM, the tpCR rates were 57.59% (HP) versus 53.93% (HPy), again showing no statistically significant difference ( P = 0.471). Subgroup analyses consistently demonstrated no significant interaction effects on tpCR across various patient strata (all P -interaction > 0.05). Safety analysis of the 520 patients revealed distinct toxicity profiles: the most frequent adverse event in the HPy group was diarrhea of any grade (83.0%), with a 13.5% incidence of grade ≥3 diarrhea. In contrast, the most common adverse event in the HP group was vomiting (53.6%). Conclusions: In this real-world study, the HP and HPy regimens achieved comparable pathologic complete response rates as neoadjuvant therapy for early HER2-positive breast cancer. The treatment choice can therefore be individualized based on their distinct toxicity profiles, with HPy associated more with diarrhea and HP with vomiting. Clinical trial information: ChiCTR2200056467.

INTRODUCTION/AIMS:Lymphoplasmapheresis (LPE) is an innovative therapy that integrates traditional plasma exchange (PE) with leukapheresis. PE is widely established as a standard treatment for myasthenia gravis (MG) crisis, but the therapeutic potential of LPE in myasthenic crisis (MC) remains unclear. Therefore, this study aimed to compare the efficacy of LPE versus PE in the management of MC. METHODS:This was a retrospective cohort study that included 86 MC patients who were treated with either LPE (n = 47) or PE (n = 39). Primary outcome indicators were total length of hospitalization, duration of mechanical ventilation (MV), and length of stay in the intensive care unit (ICU). Secondary outcome indicators included quantitative myasthenia gravis (QMG) scores at 1 and 2 months following the onset of the crisis. RESULTS:Both LPE and PE demonstrated good tolerance in the crisis treatment. Patients in the PE cohort received an average of 3.87 replacements, compared to 2.26 in the LPE cohort. Compared to PE, LPE was associated with significantly shorter durations of MV (8.50 ± 4.69 vs. 11.73 ± 4.61 days, p = 0.016) and ICU stay (11.88 ± 5.78 vs. 15.92 ± 5.54 days, p = 0.013). Functional outcomes were also better in the LPE cohort, as demonstrated by lower QMG scores at 1- and 2-months post-crisis (p < 0.05). PE and LPE effectively decreased the levels of autoantibodies against acetylcholine receptors (AChR-Ab) and inflammatory cytokines, with LPE exhibiting superior performance. DISCUSSION:In MC, LPE may be a better choice for treatment than traditional PE.

Disruption in the homeostasis of anions within organelles in cancer cells by synthetic small-molecule anion transporters may lead to significant inhibition in the proliferation of cancer cells. However, the specific impact of anion transporters on organelles, in particular on the Golgi apparatus remains to be explored. In this study, we designed and synthesized a novel series of Golgi-targeting anion transporters composed of squaramido moiety for transporting chloride anions and benzenesulfonamido group for targeting the Golgi apparatus. These compounds were able to efficiently facilitate the transport of anions across liposomal and cellular membranes, and exhibit significant cytotoxicity toward several selected cancer cells. Among them, compound 10 was the most active in efficiently disrupting the homeostasis of chloride anions specifically within the Golgi apparatus. This disruption led to profound perturbations in the structure and function of the Golgi apparatus, and triggered Golgiphagy and further apoptosis. More importantly, compound 10 displayed potent antitumor efficacy toward HepG2 xenograft mouse models, with low toxicity and minimal adverse effects on major organs. The present findings underscore the critical role of regulating the homeostasis of chloride anions within the Golgi apparatus in triggering the Golgiphagy and apoptosis of cancer cells, and thus provide a new strategy for the discovery of innovative chemotherapy for cancers.

e12609 Background: Neoadjuvant therapy is an important treatment strategy for HER-2 positive early breast cancer and Trastuzumab combined with Pertuzumab (HP) plus chemotherapy is the current standard treatment scheme. In recent years, multiple studies have revealed that the combination of Trastuzumab and Pyrotinib (HPy) has satisfactory efficacy and controllable toxic side effects. In clinical practice, how to choose a target regimen (HP or HPy) for HER-2 positive breast cancer patients is one of the key problems to be solved urgently. Methods: In this prospective, multicenter, observational real-world study (ChiCTR220056467), patients with stage II-III HER-2 positive breast cancer were assigned to the HP group or the HPy group according to the doctor's recommendation and their own wishes (specific programs include: 6 * TCbHP/6 * TCbHPy, 4 * EC-4 * THP/4 * EC-4 * THPy and 6 * THP/6 * THPy). The primary endpoint was total pathological complete response rate (tpCR, ypT0/isypN0), while the secondary endpoints were safety indicators, EFS and OS. Results: From January 2022 to December 2024, 687 patients from 10 hospitals were enrolled in the real-world study. As of now, 386 patients have completed neoadjuvant therapy and surgery with complete data, including 204 in the HP group and 182 in the HPy group, respectively. Statistical difference were observed in neoadjuvant chemotherapy and the expression levels of Ki-67. To reduce selection bias and ensure comparability of baseline data between two groups, propensity score matching (PSM) was performed in a 1:1 ratio. After PSM, 136 patients were equally divided and there was no statistically significant difference in baseline characteristic between the two groups. Before PSM, there was a statistically significant difference in tpCR rates between the HP group and the HPy group (63.24% vs 48.35%, P = 0.003); After PSM, the tpCR rate of the HPy group was consistent with that of the HP group, with no statistically significant difference (60.29% vs 61.76%, P = 0.860). Subgroup analysis showed that there was no statistically significant difference in tpCR rates between the HPy group and the HP group in each subgroup (all P interactions > 0.05). In terms of safety, 386 cases were included in the analysis, among which the most common adverse reactions in the HPy group were diarrhea (82.7%), nausea (80.4%), and vomiting (78.1%), while the most common adverse reactions in the HP group were anemia (66.7%), vomiting (55.9%), and leukopenia (49.3%). Conclusions: In the real-world study, HER-2 positive early breast cancer patients are more likely to use HP as neoadjuvant therapy, and HP are more likely to be used in combination with platinum drugs. Our study has confirmed that there is no significant difference in tpCR rates between HPy or HP. Clinical trial information: ChiCTR220056467 .

The aim of this study is to develop a prognostic model for evaluating radiotherapy response in patients diagnosed with rectal neoplasms by integrating genomic and clinical data. Publicly accessible datasets from The Cancer Genome Atlas and Gene Expression Omnibus were analyzed to identify differentially expressed genes associated with drug resistance and mitophagy. Functional enrichment analyses were conducted to investigate relevant biological pathways. A prognostic risk model was constructed using least absolute shrinkage and selection operator regression and validated via receiver operating characteristic (ROC) curve analysis and Kaplan-Meier survival analysis. The final model incorporated 15 genes selected from an initial set of 121 differentially expressed genes and demonstrated moderate to high predictive accuracy for 1-, 2-, and 3-year overall survival (area under the ROC curve: 0.70-0.90). Kaplan-Meier analysis revealed statistically significant differences in survival outcomes between high-risk and low-risk patient groups. Pathway enrichment analysis indicated that the selected genes were involved in actin cytoskeleton reorganization and antiviral immune responses. Differential expression of key genes within the model was confirmed through quantitative polymerase chain reaction assays. The resulting prognostic model enhances understanding of the molecular mechanisms underlying radiotherapy response in rectal neoplasms and may support individualized therapeutic decision-making in clinical oncology.

This study aimed to investigate the effects of Nano-cAMP on growth performance, gut development, and microbiota composition in broilers. A total of 108 21-day-old yellow-feathered female chicks were randomly divided into three groups with six replicates per group and six chicks per replicate according to the principle of consistent body weight. Experimental treatments included the following: (1) CON group (basal diet), (2) cAMP group (basal diet + 0.02 g/kg cAMP), and (3) Nano-cAMP group (basal diet + 0.37 g/kg Nano-cAMP liposomes). After a 21-day experimental period, results revealed the following: Compared with the CON group, the Nano-cAMP group exhibited a significantly reduced feed-to-gain ratio (p < 0.05). The cAMP group exhibited a significant increase in duodenal index (p < 0.05), whereas the Nano-cAMP group demonstrated greater jejunal villus height (p < 0.05). Both treatment groups showed significant upregulation of cholecystokinin (CCK) and secretin gene expression (p < 0.05). Analysis of alpha-diversity indices (Chao1, Shannon, Simpson) revealed no significant differences in jejunal and cecal microbiota composition between experimental groups (p > 0.05). Notably, the relative abundance of Firmicutes significantly increased (p < 0.05) in the cAMP and Nano-cAMP groups, whereas Proteobacteria, Gemmatimonadota, and Chloroflexi significantly decreased (p< 0.05). The combined relative abundance of three Lactobacillus genera and Bifidobacterium was obviously elevated. Linear discriminant analysis identified Bifidobacterium, Ruminococcus torques group, and uncultured_Thermoanaerobacterales_bacterium as dominant genera in the intestinal tract of Nano-cAMP group. In conclusion, dietary addition of Nano-cAMP promotes jejunal development, modulates appetite hormones mRNA expression, enhances absorption capacity, increases the relative abundance of intestinal probiotics such as Bifidobacterium and cellulose-degrading bacteria such as Ruminococcus torques group, optimizes gut microbiota composition, and ultimately reduces the feed-to-gain ratio in broilers.

INTRODUCTION:HER2-positive breast cancer is an aggressive subtype that benefits from targeted therapies. Some studies have shown that pyrotinib (P) plus trastuzumab (H) has a good efficacy against early or locally advanced HER2-positive breast cancer. However, there is still no systematic review and meta-analysis supporting the efficacy and safety of pyrotinib plus trastuzumab versus standard regimens in the neoadjuvant treatment of early or locally advanced breast cancer. This study is the first systematic review and meta-analysis to compare the efficacy and safety of pyrotinib combined with trastuzumab versus trastuzumab combined with pertuzumab (Per) and trastuzumab monotherapy in the neoadjuvant treatment of HER2-positive breast cancer. METHODS:We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, CNKI, Wan Fang and VIP databases for relevant studies published up to August 30th, 2024. RCTs, cohort studies and retrospective studies with HER2-positive breast cancer patients who had not received breast cancer-related treatments previously were included. Treatment of P + H, H or Per + H arms with chemotherapy combined with pyrotinib plus trastuzumab, trastuzumab or pertuzumab plus trastuzumab as neoadjuvant treatment. The primary outcome was the total pathological complete response (tpCR), and secondary outcomes included breast pathological complete response (bpCR), ORR, DCR, and grade III/IV AEs. The quality of evidence was assessed using the GRADE. RESULTS:A total of nine studies (4 RCTs, 1 prospective cohort study and 4 retrospective analysis) involving 1745 patients were included. The P + H arm showed no significant difference in tpCR compared to Per + H (RR: 0.94, 95 % CI: 0.80-1.11, p = 0.46) but demonstrated a significant improvement in tpCR over trastuzumab monotherapy (RR: 1.83, 95 % CI: 1.56-2.15, p < 0.001). This finding was further confirmed in meta-analysis of RCTs (RR: 1.87, 95 % CI: 1.42-2.47, p < 0.001). The P + H arm had a higher incidence of grade III/IV diarrhea (RR: 10.54, 95 % CI: 5.96-18.63, p < 0.001) but similar rates of other AEs compared to the H arm. The evidence quality for tpCR (P + H vs. H, RCT) was high, and that for tpCR (P + H vs. H) was moderate, while that for tpCR (P + H vs. Per + H) was low. CONCLUSIONS:Pyrotinib combined with trastuzumab may offer an effective neoadjuvant treatment option for HER2-positive breast cancer, with a superior efficacy over trastuzumab alone. However, pyrotinib plus trastuzumab did not show better efficacy compared with Per + H. Pyrotinib plus trastuzumab was associated with more diarrhrea than trastuzumab monotherapy. In addition, P + H is less cost-effective compared with the combination of Per + H.

OBJECTIVE:This multicenter real-world study aimed to evaluate the efficacy, safety, and neoadjuvant trastuzumab and pertuzumab combined with different chemotherapy regimens in Chinese patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS:A retrospective analysis was conducted on 557 patients treated at 15 institutions in China between January 2019 and December 2021. Patients were divided into three groups based on chemotherapy regimens: EC-THP (epirubicin, cyclophosphamide, docetaxel/paclitaxel protein-bound, trastuzumab, pertuzumab), TCbHP (docetaxel/paclitaxel protein-bound, carboplatin, trastuzumab, pertuzumab), and THP (docetaxel/paclitaxel protein-bound, trastuzumab, pertuzumab).The primary endpoint was total pathological complete response (tpCR), defined as the absence of invasive disease in both the breast and axillary lymph nodes (ypT0/is, ypN0). Secondary endpoints included axillary pCR (ypN0), breast pCR (ypT0/is), and safety. Propensity score overlap weighting was applied to minimize confounding factors. RESULTS:Of the 557 patients included in the study, 341 (61.2%) achieved tpCR. The tpCR rate was significantly higher in the HER2-positive hormone receptor (HR)-negative group (183/242 patients, 75.6%) than in the HER2-positive HR-positive group (158/315 patients, 50.2%, P < 0.001), as well as bpCR was achieved in 188/241 patients (77.7%) in the HER2-positive HR-negative group compared to 164/315 patients (52.1%) in the HER2-positive HR-positive group ( P < 0.001), and apCR was achieved in 214/242 patients (88.4%) vs. 240/315 patients (76.2%), respectively ( P < 0.001). After applying propensity score overlap weighting, no significant differences were observed among the three treatment regimen groups in tpCR (68.4% vs. 63.0% vs. 54.5%, P = 0.116), bpCR (71.3% vs. 64.0% vs. 59.6%, P = 0.198), or apCR (80.2% vs. 84.4% vs. 73.9%, P = 0.173). Gene analysis suggested favorable tpCR trends in patients with TP53, ERBB2, MYC, or CCND1 alterations, though not statistically significant. Most adverse events were grades 1-2, with anemia (254/557, 45.6%), leukopenia (147/557, 26.4%), and reduced ejection fraction (99/421, 23.4%) being the most common. No fatal toxicities were reported. CONCLUSIONS:Trastuzumab and pertuzumab combined with different chemotherapy regimens demonstrated high tpCR rates and manageable safety in HER2-positive breast cancer, particularly in HER2-positive HR-negative patients. The study supports the real-world efficacy of dual HER2-targeted neoadjuvant therapy, though further validation of biomarkers and long-term outcomes is needed.

Cancer therapy faces significant challenges due to drug resistance and the limitations of conventional treatments that primarily target single mechanisms such as apoptosis. Herein, we designed and synthesized a class of 1,2,4-triazolopyrimidinyl derivatives as multifunctional chemotherapeutic agents that trigger both ferroptosis and apoptosis. These compounds are very effective in reducing the viability of some cancer cell lines. Among them, compound 34 demonstrated a broad spectrum of antiproliferative effects against nine cancer cell lines. Compound 34 induced both ferroptosis and apoptosis by causing G2/M phase cell cycle arrest, disrupting mitochondrial membrane potentials, promoting lipid peroxidation, and increasing the levels of Ca2+ and Fe2+ through the activation of calcium/calmodulin signaling. Significantly, compound 34 suppressed tumor growth by 92% in A549 xenografts and 95% in A549/TAX xenografts with minimal toxicity. These findings might shape the rational design in a new wave of dually functioned drugs for the treatment of cancers.

Circadian rhythms play a pivotal role in regulating diverse physiological functions, notably the composition and activity of gut microbiota. Accumulating evidence indicates that circadian rhythm disruption can induce dysbiosis of the gut microbiome, which in turn is implicated in influencing the tumor microenvironment (TME) and facilitating cancer progression. This review integrates and analyzes recent advances elucidating the complex interplay where circadian rhythms modulate gut microbiota, and how these circadian-driven microbial changes affect the TME. This review analyzes recent advances in elucidating the complex interplay among circadian rhythms, gut microbiota, and the TME. We examine how circadian disruption modifies the diversity and metabolic functions of gut microbiota, resulting in alterations of microbial metabolites, including but not limited to short-chain fatty acids and secondary bile acids. These metabolic alterations have the potential to modulate immune cell function, vascular remodeling, and tumor cell metabolism within the TME. We investigate the potential mechanisms through which gut microbial dysbiosis induced by circadian misalignment could promote an immunosuppressive TME and accelerate tumor growth. Additionally, we evaluate emerging therapeutic strategies that leverage the circadian-microbiome axis, encompassing chronotherapy, probiotic supplementation, and fecal microbiota transplantation. The integration of circadian biology, microbiology, and cancer immunology presents promising avenues for the development of novel diagnostic and therapeutic approaches. However, significant challenges persist in translating these findings into viable clinical applications. Further research is imperative to elucidate the molecular pathways interconnecting circadian rhythms, gut microbiota, and the TME, and to develop personalized chronobiological interventions for cancer prevention and treatment.

Potassium channel tetramerization domain-containing 1 (KCTD1) plays a critical role in transcriptional regulation and adipogenesis, but its significance in hepatocellular cancer (HCC) has not been reported. Immunohistochemistry, Western blotting and quantitative real-time PCR analysis were performed to assess the expression of KCTD1 and related genes in HCC cells. MTT assays, colony formation, cell migration, invasion and the in-vivo mouse models were utilized to evaluate the function of KCTD1 in HCC progression. Co-immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assays were conducted to elucidate the molecular mechanisms of KCTD1 in HCC. KCTD1 expression was increased in human HCC tissues and closely associated with advanced tumor stages. KCTD1 overexpression enhanced growth, migration, and invasion of Huh7 and HepG2 cells both in vitro and in vivo, while KCTD1 knockdown reversed these effects in MHCC97H cells. Mechanistically, KCTD1 interacted with hypoxia-inducible factor 1 alpha (HIF-1α) and enhanced HIF-1α protein stability with the inhibited prolyl-hydroxylases (PHD)/Von Hippel-Lindau (VHL) pathway, consequently activating the Vascular Endothelial Growth Factor (VEGF)/VEGFR2 pathway in HCC cells. Sorafenib and KCTD1 knockdown synergistically inhibited intrahepatic tumor growth following in situ injection of MHCC97H cells. miR-129-5p downregulated KCTD1 by binding to KCTD1 3′UTR. Finally, 45 µg exosomes from miR-129-5p-overexpressing MHCC97H cells combined with 25 mg/kg sorafenib to decrease HCC tumor size. These results suggested that KCTD1 protects HIF-1α from degradation and activates the VEGF signaling cascade to enhance HCC progression. Therefore, KCTD1 may serve as a novel target of HCC and pave the way for an efficient combined therapy in advanced HCC.

ObjectiveTo identify adverse event (ADE) signals of three tyrosine kinase inhibitors (TKIs) (Tucatinib, Lapatinib, and Neratinib) used for HER-2 positive breast cancer by utilizing the FAERS database, and to analyze their safety profiles to provide references for clinical risk management.MethodsData from the FAERS database spanning Q1 2015 to Q3 2024 were retrieved, including reports where Tucatinib, Lapatinib, or Neratinib was identified as the primary suspect drug. Disproportionality analysis (ROR, PRR) and the Comprehensive Standard method were employed to detect potential ADE signals. The distribution of ADEs across different System Organ Classifications (SOCs) was also analyzed.ResultsA total of 7,848 ADE reports were analyzed, identifying 557 significant signals. The primary ADEs were concentrated in gastrointestinal disorders, general conditions, administration site reactions, and skin and subcutaneous tissue disorders. Neratinib exhibited higher gastrointestinal toxicity, Lapatinib was associated with notable skin toxicities, and Tucatinib showed specific adverse reactions linked to combination therapies.ConclusionThe three TKIs demonstrated distinct ADE signal profiles, with gastrointestinal, systemic, and skin toxicities being the major areas of concern. Future research should validate these findings and develop effective management strategies to enhance treatment safety and improve the quality of life for HER-2 positive breast cancer patients.