Browse Articles
Discover research articles across all indexed journals
Association of <i>ESR1</i> amplification with survival and benefit from CDK4/6 inhibition in breast cancer.
1093 Background: While ESR1 mutations are established mediators of endocrine resistance in breast cancer (BC), the significance of ESR1 amplification (amp) remains poorly understood with reported amp rates vary widely due to platform-specific differences. We leveraged a large clinico-genomic real-world database and applied a stringent NextGen sequencing (NGS) approach to test ESR1 amp. We identify ESR1 amp as a molecular entity distinct from canonical estrogen-driven resistance mechanisms. Methods: Breast tumors underwent NGS of DNA and RNA (WES/WTS; NextSeq and NovaSeq; Caris Life Sciences, Phoenix, AZ). Gene copy number was determined by CNVKit with >=6.0 copies defined as amp to identify focal, high-level copy number events, minimizing misclassification of chromosome 6 copy gains. Real-world clinical data were obtained from insurance claims. Time on treatment (TOT) was defined treatment start to end; overall survival (OS) from tissue collection to last contact. Cox proportional hazards model and log-rank tests were used for survival analysis. Molecular comparisons used χ² or Mann-Whitney U with multiple-testing adjustment (q<0.05). Gene set enrichment analysis was performed, with significance defined as FDR<0.05. Results: Among 27,979 BC tumors, 165 were ESR1 amp (0.6%), a prevalence much lower than prior reports. ESR1 amp was significantly enriched in the Luminal B (LumB) subtype (1.4%, 81/5,915) versus other subtypes (0.1–0.4%, p<0.0001). ESR1 amp tumors exhibited features of genomic instability, including higher genomic loss of heterozygosity (61% vs 24%), TP53 mutations (59% vs 27%), and amplifications on chromosomes 6, 8, and 11 (q<0.05). Transcriptomically, ESR1 amp tumors had significant enrichment of G2M checkpoint and MYC target gene sets by GSEA in the overall cohort (G2M NES 2.61, MYC NES 2.41,) and in LumB (G2M NES 3.18; MYC NES 3.04, all FDR<0.001), consistent with CDK4/6-independent cell-cycle progression. Unlike ESR1 mutations, ESR1 amplification was not associated with increased GREB1 expression (4.4 vs 4.2 TPM, p>0.05), consistent with the absence of estrogen-response pathway enrichment. Clinically, ESR1 amp was associated with reduced OS in the overall cohort (HR 1.296, p=0.016) and LumB subset (HR 1.43, p=0.009). Palbociclib TOT was significantly shorter in ESR1 amp vs. non-amp tumors (all BC: 7.0 vs 11.0 months, HR 1.39 [95% CI 1.045–1.85], p=0.023; LumB: 4.9 vs 11.4 m, HR 1.57 [1.1–2.2], p=0.01). This effect was significant after adjusting for TP53, gLOH, and CDH1 alterations (adjusted HR 1.47 [1.04–2.06], p=0.027). No TOT difference was observed with aromatase inhibitors. Conclusions: In this large real-world analysis, ESR1 amplification defines a rare, genomically unstable breast cancer subset with proliferative signaling and reduced clinical benefit from CDK4/6 inhibition, supporting its potential role as a negative predictive biomarker.
Chemotherapy-induced gut microbiota taxonomic deviation and its association with outcomes and toxicities in breast cancer: CANTO microbiota.
2589 Background: Gut microbiota (GM) modulates immunotherapy (IT) efficacy and toxicity, but its impact on outcomes in breast cancer (BC) patients (pts) remains unclear. TOPOSCORE is a GM-derived score reflecting the ecosystem structure that classifies pts into SIG1+ or SIG2+ profiles, the latter being enriched in obligate anaerobes with immunostimulatory proprieties and associated with favorable IT outcomes. Methods: CANTO-Microbiota (target N=1000) is an ongoing substudy of the prospective CANTO cohort (NCT01993498). Stool samples were available from 209 pts (202 pre-treatment (Tx) and 94 post-Tx [after surgery, chemotherapy (CT) ±targeted-, and/or radiotherapy]), enrolled 2015-2024. GM was profiled by shotgun metagenomics and assessed as TOPOSCORE (SIG1+ vs. SIG2+) pre- and post-Tx. Associations of GM with invasive (iDFS), distant disease-free (DDFS), and overall survival (OS) (Kaplan–Meier and Cox regression models), and with treatment-related toxicities (multivariable logistic regression). Post-treatment analyses were landmark-based. Results: Median age was 46.6 years, 72% were premenopausal, 79% had stage II-III, 36% HER2+, 34% HR+/HER2-, and 30% TN, 89% received (neo)adjuvant CT, 15% IT and 33% anti-HER2-therapy. Median follow-up was 2.2 years. At baseline, 74% of pts had a SIG2+ profile. This profile was not associated with clinicopathologic features or clinical outcomes; however, SIG2+ was associated with a reduced incidence of post-treatment diarrhea and long-term neuropathy, and remained independently protective against neuropathy (OR 0.25, 95% CI 0.09–0.64; p=0.005). Paired analyses (n=87) revealed a significant shift in TOPOSCORE signatures post-treatment, resulting in an increase in SIG1+ prevalence from 28% to 47% (p=0.004), In univariable landmark Cox analyses, post-treatment SIG1+ was associated with worse iDFS (HR 5.0, 95% CI 1.1–4.2; p=0.04), DDFS (p=0.0053) and OS (p=0.04). In multivariate model adjusted for age, stage, and subtype, post-treatment SIG2+ remained independently protective for iDFS (HR 0.17, 95% CI 0.03–0.88; p=0.035). Assessing longitudinal GM trajectories, worsening patterns (SIG2+→SIG1+ in 28% and persistent SIG1+→SIG1+ in 20% of pts ) were associated with an increased risk of iDFS (HR 5.25, 95% CI 1.11–24.7; p = 0.036). Post-treatment TOPOSCORE associations with outcomes were validated in two independent prospective cohorts outside France. Conclusions: Chemotherapy is associated with measurable shifts in GM composition that correlated with treatment-related long-term toxicity and outcomes. These findings support the evaluation of microbiota centered interventions during treatment in eBC.
High expression of CIITA, the master MHC-II regulator, as a predictor of survival benefit from immune checkpoint inhibitors across solid tumors.
e14589 Background: The class II major histocompatibility complex transactivator (CIITA) is the master regulator of MHC class II expression and a potential determinant of tumor immunogenicity. However, its prevalence, immunologic correlates, and association with immune checkpoint inhibitor (ICI) outcomes in solid tumors remain incompletely defined. We characterized CIITA expression patterns, immune features, and clinical outcomes in a large real-world pan-cancer cohort. Methods: We analyzed 514 patients with advanced solid tumors profiled by RNA sequencing performed in a clinical laboratory (OmniSeq INSIGHT, Buffalo, NY). CIITA-high tumors were defined as those in the ≥75th percentile (n = 107). Associations between CIITA-high status and immune biomarkers were evaluated using univariable and multivariable logistic regression. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier methods and Cox proportional hazards models in the full cohort, in ICI-treated patients, and in patients who never received ICIs. Results: High CIITA expression was observed in 20.8% of patients. Ovarian cancer demonstrated the strongest enrichment (35% in CIITA-high vs 20% in CIITA-low), with a multivariable odds ratio (OR) of 3.31 (95% CI, 1.02–10.8; p = 0.047). High CIITA expression was strongly associated with increased expression of multiple immune checkpoint molecules (PD-1, PD-L1, PD-L2, CTLA4, LAG3, TIM3, BTLA) and HLA class II molecules (ORs 4–30) (all p < 0.01, univariate). Several MHC II–related HLA genes, including HLA-DOA, HLA-DOB, HLA-DMA, HLA-DMB, and HLA-DQB2, remained independently associated with CIITA-high status in multivariable analyses. Among 217 patients treated with ICIs, CIITA-high was associated with markedly improved OS (median 3.64 vs 1.18 years; multivariable p = 0.02). No survival difference was observed in 272 patients who never received ICIs (median 3.91 vs 3.50 years; p = 0.30). Conclusions: CIITA-high tumors represent a distinct immune-active subgroup characterized by widespread upregulation of checkpoint and antigen-presentation pathways. CIITA-high status correlates significantly and independently with substantial survival benefit in patients receiving ICIs, but not in those treated without ICIs. CIITA may serve as an emerging, biologically grounded biomarker for predicting ICI responsiveness across solid tumors.
Clinical utility of discordances between histomorphology and molecular biomarkers in precision oncology.
3005 Background: Conventional molecular biomarkers guide treatment selection in precision oncology, yet therapeutic benefit remains variable even within biomarker-defined populations. Deep learning (DL) models can infer biomarker status from hematoxylin and eosin (H&E) histopathology, but systematic discordances arise between conventional biomarker assays and their histomorphology-based (HM) predictions. We hypothesized that such discordances reflect biologically meaningful tumor functional states rather than model error and may have clinical relevance. Methods: DL models were trained to predict 15 clinically relevant biomarkers from H&E images across six cancer types using public datasets. Discordant cases, defined as disagreement between assay-based biomarker labels and their DL prediction from H&E, were quantified and analyzed for alignment with functional gene expression states and clinical outcomes. Clinical utility was assessed in two landmark randomized trials: FINHER (HER2 prediction; N = 1010; trastuzumab randomized in HER2+ patients), and TAILORx (Oncotype DX recurrence score [RS] prediction; N = 10,273; chemotherapy randomization within RS 11–25). Adjusted Cox models tested added prognostic value and treatment beneft interactions. Primary endpoint was distant recurrence. Results: Models achieved strong performance for predicting the biomarkers (median AUC 0.78; range 0.65–0.87). Discordance rates ranged from 8% (MSI in colon) to 32% (KRAS in lung). In discordant cases, HM predictions correlated more strongly with functional gene expression states than the biomarker status they were trained to predict (mean Spearman r = 0.52 vs 0.31; p < 0.001). In FINHER, predicted HER2 status added prognostic value beyond HER2 status (p = 0.01) and predicted trastuzumab benefit in HER2+ patients (p-interaction = 0.026). In HER2+ patients, trastuzumab benefit was observed in those predicted as HER2+ (HR = 0.35, 95% CI: 0.15–0.83), but not in those predicted as HER2- (HR = 1.17, 95% CI: 0.45–3.02). In TAILORx, predicted RS added prognostic value over true RS in the no-chemo group (p = 0.005) and showed treatment interaction beyond RS within RS 11–25 (N = 1629; p-interaction = 0.021), as well as when restricted to postmenopausals (p = 0.029). Discordant patients (RS 11–25 predicted as RS > 26) derived chemotherapy benefit (HR = 0.30, 95% CI: 0.13–0.77), whereas those predicted as RS < 26 did not (HR = 0.95, 95% CI: 0.71–1.29). Conclusions: Discordances between molecular biomarkers and HM predictions are not random errors but reflect underlying tumor functional states. HM biomarkers may capture relevant information missed by standard assays that can improve therapeutic benefit prediction. This framework enables reinterpretation of DL pathology predictions, supports integrating H&E models to complement biomarkers, and enables derivation of functional information without outcome data.
Molecular subtypes and lymph-node metastasis in endometrial cancer: An updated systematic review and meta-analysis.
e17643 Background: Prognostic stratification of endometrial cancer has improved with the incorporation of molecular classification into staging. Although previous meta-analyses have assessed the impact of lymph node metastasis (LNM) in the management of endometrial cancer, these studies predate the 2023 FIGO molecular staging system and the widespread use of sentinel lymph node (SLN) mapping. It remains unclear how these advances affect LNM rates in modern surgical practice. Methods: We performed a systematic review and meta-analysis of studies reporting lymph node status according to TCGA/ProMisE molecular subtypes, including POLE-mutated, MMR-deficient, No Specific Molecular Profile (NSMP), and p53-abnormal tumors. A random-effects model was used to estimate pooled LNM proportions. Sensitivity and publication-bias analyses were conducted in prespecified subgroups comparing SLN mapping with lymphadenectomy (LAD). Results: Twenty-one studies encompassing 8,963 patients were included. The prevalence of LNM varied substantially across molecular subtypes. p53-abnormal tumors demonstrated the highest pooled LNM rate (24%, 95% CI 17–32%), followed by MMR-deficient (15%, 95% CI 11–20%) and NSMP tumors (10%, 95% CI 7–14%). POLE-mutated tumors had the lowest LNM rate (9%, 95% CI 6–14%). Findings were robust across leave-one-out sensitivity analyses. Importantly, LNM rates did not differ significantly between SLN and LAD cohorts across molecular subtypes. Conclusions: Molecular classification provides clinically meaningful prognostic information beyond traditional histopathological factors and is strongly associated with the risk of LNM in endometrial cancer. The marked difference in nodal involvement between POLE-mutated and p53-abnormal tumors supports a more tailored approach to surgical staging. These findings also validate the reliability of SLN mapping for molecular risk stratification, supporting its use as a standard staging strategy.
Pan-cancer analysis of STAT6 expression and its relationship with tumor microenvironment characteristics and survival.
2585 Background: Co-targetable immune pathways influence cancer outcomes and responses to immune checkpoint inhibitors (ICIs). We examined the transcriptomic expression and clinical significance of signal transducer and activator of transcription-6 (STAT6), an immune-modulatory signaling factor activated by IL-4 and IL13 and involved in innate immunity in infection and cancer. Methods: Transcriptomic expression across 395 genes was measured in various solid tumors from 514 patients with advanced cancer, normalized to a reference population (n=735), and reported as percentiles (high defined as ≥75th percentile). We evaluated association between high STAT6 expression and transcriptomic expression of STAT6-related markers (IL4, IL13, TGFB1, IL10, CD8, CCL18, TNFRSF14 [HVEM], VISTA) and currently targetable immune checkpoints (PD-1, PD-L1, PD-L2, CTLA-4, LAG3). Genomic alterations were also assessed for the association with high STAT6 expression. Variables with P<0.2 in univariable analysis were included in the subsequent multivariable logistic regression model incorporating genomic, immunomic, and clinical factors. Clinical outcomes were evaluated using Kaplan–Meier method and Cox regression model. Results: High STAT6 expression was observed in 184 patients (35.8%); 2 (0.4%) had zero measurable expression. High STAT6 was associated with TMB <10 muts/Mb, high expression of LAG3, PD-L2, IL13, TNFRSF14 (HVEM), and VISTA (all immunosuppressive), and a diagnosis of colorectal cancer in multivariable analysis. Breast cancer was negatively associated with high STAT6. In univariable analysis, alterations in SMAD4, KRAS, and APC were significantly associated with high STAT6, though none remained significant in the multivariable model. In advanced cancer patients, high STAT6 was associated with shorter survival (N=489 with clinical data curated, Hazard ratio 1.44, 95% confidence interval 1.03–2.02, p=0.034). Among 217 ICI-treated patients, high STAT6 did not correlate with survival. Conclusions: High STAT6 expression associates with a biologically coherent tumor microenvironment characterized by factors mediating profound immune suppression. The STAT6-high phenotype is mechanistically linked to an exhausted immune landscape, evidenced by the co-expression of inhibitory checkpoints LAG3 and VISTA, and may be further driven by an IL13/STAT6 autocrine loop. Clinically, high STAT6 correlates with shorter survival in patients with advanced cancers. Prospective validation of this STAT6-driven signature is warranted to guide the development of precision therapy trials aimed at co-targeting this pathway to improve outcomes.
LAP-NET1: Results of a phase 1b evaluating NP137, an inhibitor of the epithelial-to-mesenchymal transition, in combination with mFOLFIRINOX for the first-line treatment of locally advanced pancreatic ductal adenocarcinoma.
4197 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by aggressive tumor dissemination and resistance to therapy; processes significantly driven by the epithelial-to-mesenchymal transition (EMT). Netrin-1 is a key regulator for EMT. NP137, an anti-netrin-1 antibody, has shown to inhibit EMT in preclinical models and in a phase 1 monotherapy trial. Methods: LAPNET-01 (NCT06203821) is a single arm phase Ib clinical study to assess the combination of NP137 with mFOLFIRINOX in naive locally advanced unresectable PDAC. A safety lead-in (3–12 pts, 3+3 design, NP137 14 vs 9 mg/kg) was followed by a 40-patient expansion. Treatment consisted of NP137 + mFOLFIRINOX every 2 weeks, up to 12 cycles. The primary endpoint was safety at 6 months (all-grade and grade 3/4 adverse events [AEs], CTCAE v5.0). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), surgical conversion rate and exploratory transcriptomic analyses. Laser capture microdissection was performed on 22 pre-treatment and 6 surgery samples to allow microbulk RNA sequencing. Immunohistochemistry was also performed on pre-treatment samples. Results: A total of 43 patients were enrolled in this trial. NP137 was well tolerated. AE occurred in 100% of patients (58% grade ≥ 3). ORR and disease control rate were 29% and 95%. Median PFS was 10.9 months (95% CI, 10.0 – 15.6) and median OS was 16.4 months (95% CI, 12.8 – NR) with 21 patients still alive at time of the data cut-off. Surgery was made possible in 23% of patients. Microbulk RNA sequencing revealed that the main pathway downregulated with the combination mFOLFIRINOX+NP137 is EMT, bringing a clinical validation of the main mechanism of action of NP137. Moreover, patients with tumors expressing high levels of the netrin-1 receptor neogenin (high-NEO1) at baseline (both at the RNA and proteic level (IHC)) demonstrated an improved outcomes compared to the low-NEO1 subgroup including longer median PFS (15.7 vs 10.2 months, p = 0.01) and longer median OS (not reached vs 16.5, p = 0.024). These results are consistent with experimental data demonstrating the implication of NEO1 in PDAC EMT and its progression. Conclusions: NP137 in combination with mFOLFIRINOX demonstrates a favorable safety profile, promising clinical activity and a mechanistically distinct mode of action supported by translational analyses. These results warrant further investigation of netrin-1 blockade in randomized trials and provide a rationale for biomarker-driven development of NP137 in PDAC. Further work is ongoing to better characterize the distribution of NEO1 in first-line unresectable PDAC. Clinical trial information: NCT06203821 .
Utilizing a resident-led elective to improve the understanding of cancer prevention and survivorship among internal medicine residents.
e21006 Background: Advances in cancer screening, early detection, and targeted therapies have increased the number of cancer survivors in the United States to 18.1 million as of 2022 1 , creating a patient population with complex medical, psychosocial, and financial needs. Despite this, formal training in cancer survivorship is often lacking in internal medicine residency programs. To address this unmet educational need, residents in the Brown University Internal Medicine Program developed the “Cancer Prevention & Survivorship Elective,” which formally launched in 2023. The elective is designed to enhance internal medicine residents’ understanding of cancer prevention and survivorship and is offered annually, with its fourth iteration underway as of January 2026. Methods: Between 2023 and 2025, 28 internal medicine residents completed the month-long elective. During the elective, residents participate in multiple didactics and rotate through clinics in disciplines such as onco-psychiatry, onco-fertility, palliative care, complementary medicine, and physical medicine and rehabilitation. Participants completed anonymous pre- (n=25) and post-elective (n=16) surveys assessing confidence in cancer prevention and survivorship on a 5-point Likert scale (1 = very unconfident, 5 = very confident). Pre- and post-elective responses were compared using the Mann-Whitney U test, with statistical significance defined as p < 0.05. Results: Median confidence in cancer prevention increased from 3 (neutral) pre-elective to 4 (confident) post-elective (one-tailed Mann-Whitney U = 30.5, p < 0.001). Similarly, median confidence in cancer survivorship rose from 3 to 4 (U = 18.5, p < 0.001), representing a statistically significant improvement in residents’ self-assessed competency in both domains. Additional descriptive data are summarized in the table below. Conclusions: An annual elective in cancer prevention and survivorship significantly improved internal medicine residents’ confidence in these domains. In the context of ongoing gaps in survivorship care, these findings support survivorship-focused education as a scalable approach to strengthening oncology training within internal medicine residency programs. Expansion to additional trainee groups and continued curricular refinement may further enhance oncology education in residency. References: American Cancer Society. Cancer Treatment & Survivorship Facts & Figures 2022-2024. Atlanta: American Cancer Society; 2022. Pre-Elective (n=25) Post-Elective (n=16) Domain Confidence Rating* (Mean ± SD) Confidence Rating* (Mean ± SD) Mean Difference (Post - Pre) Cancer Prevention 2.84 ± 0.69 4.25 ± 0.58 1.41 Cancer Survivorship 2.44 ± 0.77 4.19 ± 0.66 1.75 *1 = very unconfident, 2 = unconfident, 3 = neutral, 4 = confident, 5 = very confident.
Association between resilience and financial toxicity: The role of age, education, and health insurance.
e24124 Background: Women with metastatic breast cancer (MBC) are at high risk of financial toxicity (i.e., disturbed financial well-being). Resilience has been identified as a key protective factor associated with better overall quality of life among cancer population. However, whether resilience is associated with lower financial toxicity is unknown. We sought to examine the association between resilience and financial toxicity in women with MBC and explore age, education and health insurance as potential moderators of this association. Methods: We analyzed cross-sectional data from women with MBC ( N = 209) who completed self-reported questionnaires of Resilience Scale Specific to Cancer (RS-SC), Comprehensive Score for Financial Toxicity (COST-FACIT). COST-FACIT included 11 items rated on a five-point Likert scale (0-4), total score ranged from 0-44 with higher scores indicating better financial well-being (lower financial toxicity). Participants (n = 2) with missing data were excluded from analysis. We conducted multiple linear regression to analyze the association of resilience with financial toxicity. Interaction terms were used to test moderating effects of age (18-39, 40-64 and ≥65 years), education (high school/Some college vs. college/master’s degree or above) and health insurance (public vs. private/marketplace insurance). We adjusted for marital status, income, employment status, time since MBC diagnosis, and treatment types as covariates. Results: Of 209 women, 56.5% were aged 40-64 years, 76.6% were White, and 79.9% had a college or master’s degree or above. The mean RS-SC score was 34.49 ( SD = 6.67) and COST-FACIT score was 20.81 ( SD = 10.67). Adjusting for covariates, higher resilience was linked to better financial well-being (β = 0.21 [95%CI: 0.09, 0.33], P < 0.001). Education (β = 0.28, P = 0.027) and health insurance (β = 0.27, P = 0.025) moderated this relationship, with resilience more strongly associated with better financial well-being among those with college/master’s degree or above and private insurance than other groups. Age did not moderate this association. Conclusions: Women MBC who have higher resilience are more likely to experience better financial well-being, but the strength of this association varied by socioeconomic factors. Further research is needed to determine this finding in longitudinal studies. Our results have important implications for incorporating resilience into financial toxicity interventions and tailoring such interventions based on individuals’ socioeconomic characteristics.
Continual depletion of circulating tumor cells using an automated device enriched with affinity glass bead substrates in breast and CRC patient’s whole blood.
e12505 Background: Despite no evidence of disease radiologically or pathologically, about 25-50% colorectal (CRC) Stage II-III and early stage breast cancer (BC) cases are known to recur. Presence of circulating tumor cells (CTCs) having EMT traits represents aggressive disease systemically. Upon autonomous oncogenic activation, epithelial cells acquire invasiveness to form metastasis. High EMT score with immune checkpoints, like PD-L1 expression, could evade immune system. Following curative-intent surgery and treatments, CTCs represent minimal cellular residual disease (MCRD) with strong predictor for recurrence. We present automated extracorporeal device, to capture, analyze, and deplete CTC for further analysis. Methods: We retrospectively analyzed 66, CRC stage II-III (n=41) and BC (n=25) patients. Whole blood was processed to deplete CTCs using OncoMetastat device. In 41 CRC patients, 12 were female and 29 were male. The average patient age for BC and CRC patients was 53.6 and 58, respectively. Device consists of spiral channel (127 × 85 × 5 mm; spiral span: 66 mm and width: 4 mm), 3D-printed using biocompatible resin, filled with anti-EpCAM antibody conjugated glass beads (GB). Device possess controller, peristaltic pump for blood circulation in and out from spiral channels. Vibrational-energy imparted motion to GB. We analyzed hemolysis, protein, and leucocyte adsorption, and CTC capture in the device. CTC capture efficiency was compared with OncoDiscover CTC technology approved by CDSCO, India. Blood was pumped in device and incubated with affinity enriched GBs for 30 min, under constant vibration (200 Hz) to enhance CTC capture and prevent blood stagnancy. CTCs were confirmed for CK18+ve, DAPI+ve and CD45-ve and analyzed using an automated fluorescence microscope. Results: A total of 48 CTCs were detected in 58% (38/66) of patients. CTC +ve was higher in BC patients (60.0%) over CRC patients (56.1%). Total mean CTC distribution was 0.73, with CRC 0.73 and BC 0.72, respectively. The NPV was determined to be 0.86 (86%). Auto-scan imaging demonstrated 100% efficiency in detecting CTCs. We observed low leukocyte adhesion with anti-EpCAM GB. WBCs counts varied by cancer type (mean WBC count/ml of 4.9 × 10 6 ; Breast CA, 3.9 × 10 6 ; Colorectal CA), lower compared to healthy controls (6.9 × 10 6 ). Clinically insignificant hemolysis (<1%) and protein-binding (~1.5%) was noted in the spiral channel. GBs with vibrational-energy showed enhanced CTC sequestration (>90% cell capture efficiency) compared to vibration-free. Conclusions: We show efficiency of CTC depletion in 66 CRC and BC patients using an automated device. Early stage CRC and BC patients having CTCs possess high risk of progression of distant metastasis. Thus, post complete remission (CR), using an extracorporeal device to deplete CTCs could reduce the risk of metastasis.
Clinical impact and molecular profiling of <i>PTEN</i> loss and <i>TMPRSS2:ERG</i> fusion in metastatic hormone-sensitive prostate cancer.
5101 Background: PTEN loss in prostate cancer (PC) is associated with aggressive disease and resistance to conventional treatments. TMPRSS2:ERG fusion (TE+) is one of the most frequent genomic alterations in PC and frequently co-occurs with PTEN loss, yet the clinical impact of this association remains unclear. The aim of the present study is to evaluate clinical outcomes in metastatic hormone-sensitive PC (mHSPC) patients (pts) stratified by TE and PTEN status and to characterize associated gene expression signatures. Methods: We conducted a multicenter ambispective study enrolling mHSPC pts receiving different treatment strategies. The primary objective was to evaluate castration resistant PC-free survival (CRPC-FS) according to PTEN and TE. TE fusion and PTEN status were assessed in FFPE tumor samples using mRNA expression profiling by nCounter. PTEN low was defined with a previously validated cut-off (Jimenez, Eur Urol Onc 2023). RNA-seq analysis was performed to molecularly characterize PTEN low and TE associated transcriptional profiles using gene set variation analysis. Results: A total of 295 pts were included; median age was 72.9 years, 46.1% had high-volume disease and 66.8% presented de novo stage IV disease. Treatment consisted of androgen deprivation therapy (ADT) plus abiraterone (n=97), apalutamide (n=157), enzalutamide (n=41). Overall, 74 pts were PTEN low and 90 pts were TE+. There were no significant differences in baseline characteristics according to PTEN or TE. Among PTEN low pts, 33 (44.6%) were TE+. There was a positive correlation between PTEN low and TE+ ( p =0.01). With a median follow-up of 31.9 months (range 0.8 – 91.3), 32% of pts progressed to CPRC and 31.2% died. In the overall cohort, PTEN low /TE- tumors (14.1%) were associated with the poorest clinical outcomes, showing significantly inferior CRPC-free survival (HR 2.1, p =0.0027) and overall survival (HR 2.1, p =0.0058). Within the PTEN low subgroup, TE+ tumors demonstrated significantly improved CRPC-FS compared with TE- negative tumors (HR 0.45, p =0.04), with a non-significant trend toward improved overall survival (HR 0.48, p=0.07). In the 35 pts with RNA-seq analysis, PTEN low /TE- tumors were characterized by enrichment of DNA repair and neuroendocrine and EZH2 signatures ( p =0.04 and p= 0.03 respectively). PTEN low /TE+ had enrichment of PI3K signaling ( p =0.01) and epithelial differentiation ( p =0.05). Androgen-response hallmark was infraexpressed in PTEN low tumors regardless of TE status. Conclusions: PTEN low /TE- tumors exhibited the worst clinical outcomes, while TE+ in PTEN low disease partially rescued the adverse phenotype. Combined PTEN and TE stratification may therefore inform risk-adapted treatment escalation and intensification strategies.
SYS6010 combined with SYH2051 in advanced solid tumors: Results from a phase Ib/II trial.
4044 Background: SYS6010 is an antibody-drug conjugate (ADC) composed of an epidermal growth factor receptor (EGFR)-specific antibody, a cleavable linker, and the topoisomerase I inhibitor JS-1. SYH2051 is an ATM inhibitor that disrupts DNA repair. The combination of SYS6010 and SYH2051 has shown preliminary antitumor activity (ASCO 2025) in advanced gastrointestinal tumors, particularly gastric cancer (GC). Here, we report the safety and preliminary efficacy of SYS6010 plus SYH2051 in patients with advanced solid tumors in phase Ⅰb. Methods: This was a multi-center, open-label study. Phase Ⅰb enrolled patients with advanced, EGFR-positive or EGFR-mutant solid tumors, including gastric cancer (GC) with EGFR expression (≥1+) in ≥30% of tumor cells, who were refractory or intolerant to standard treatment. Phase Ⅰb consisted of dose escalation and expansion parts. Dose escalation followed a 3+3 design, exploring SYS6010 at doses of 3.2 mg/kg and 3.6 mg/kg (both Q2W) in combination with SYH2051 at 20 mg, 40 mg, 60 mg, and 80 mg (QD). The primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase Ⅱ dose (RP2D). Results: As of October 31, 2025, a total of 117 patients (median age, 58 years; male, 73.5%; ECOG PS 1, 72.6%; metastasis, 100%) were enrolled. Most common tumor types included gastric cancer (GC, n = 66), colon cancer (n = 24), and rectal cancer (n = 15). One dose-limiting toxicity (grade 4 thrombocytopenia) was reported in the regimen of SYS6010 3.2 mg/kg plus SYH2051 60 mg. The RP2D was determined to be SYS6010 3.6 mg/kg plus SYH2051 40 mg. Overall, 94.0% (110/117) of enrolled patients reported at least one treatment-related adverse event (TRAE). The common TRAEs (≥30%) were anemia (68.4%), leukopenia (50.4%), neutropenia (48.7%), decreased appetite (47.0%), nausea (43.6%), hypoalbuminemia (40.2%), fatigue (39.3%), and thrombocytopenia (33.3%). Grade ≥ 3 TRAEs occurred in 44.4% (52/117) of patients. Treatment discontinuations due to TRAEs were reported in 0.9% (1/117) of patients for SYS6010 and in 0.9% (1/117) for SYH2051. No deaths were reported due to TRAEs. Among all efficacy-evaluable GC patients treated with the RP2D regimen (n = 33), the confirmed objective response rate (cORR) was 15.2%, disease control rate (DCR) was 69.7%, and median progression-free survival (mPFS) was 4.5 mo (95% CI, 2.1–5.7). For the 17 patients receiving RP2D regimen as ≥3rd-line therapy, cORR was 23.5%, DCR was 88.2%, and mPFS was 5.4 mo (95% CI, 2.5–NR). The 3-mo and 6-mo PFS rates were 72.4% and 36.2%, respectively. Overall survival data were immature. Conclusions: The combination of SYS6010 and SYH2051 showed acceptable safety and tolerability in patients with advanced solid tumors. Promising antitumor activity was observed in patients with advanced GC, particularly among those receiving the regimen as ≥3rd-line therapy. Clinical trial information: NCT07104877 .
Real-world utilization patterns and adverse events among patients receiving antibody–drug conjugates (ADCs) across the University of California health system.
11118 Background: Antibody–drug conjugates (ADCs) have rapidly expanded across oncology indications, yet real-world safety profiles remain incompletely characterized. Pivotal trials may not fully capture adverse events (AEs) associated with real-world treatment patterns, such as cumulative exposure or sequential ADC therapy. Methods: We performed a retrospective cohort study across six UC medical centers using de-identified structured EHR data from the University of California Health Data Warehouse (UCHDW). We included adult patients who received at least 1 dose of ADC between Jan 2015 and Feb 2025. Observational period for safety surveillance is at least 8 months. Key safety outcomes were the incidence and timing of key AEs following ADC initiation. Secondary outcomes included duration of ADC therapy and the frequency of sequential ADC. Descriptive statistics were used to analyze toxicity and time to AE of special interest. Results: Across the UC system, 4,531 patients received at least one ADC and had a documented cancer-related diagnosis, 82.7% of patients had metastatic cancer at initiation of ADC. Breast cancer was the most frequently observed cancer type (38.8%), followed by hematologic malignancies (28.5%) and bladder/urothelial cancers (11.2%). Mean dose number was 10.1 (standard deviation: 11.3). Among 4,531 ADC-treated patients, 10.6% transitioned to a second ADC, and 78.9% received concomitant anticancer therapy, including immune checkpoint inhibitors (38.0%), ICI plus chemotherapy (21.8%), or chemotherapy alone (18.7%). Incident neurotoxicity was the most frequent AE (728 patients, 16.1%), followed by hematologic (15.0%) and cardiotoxicity (14.6%) AEs. Incident ocular toxicity was observed in 343 patients (7.5%) with a median time to onset of 84 days, and incident mononeuritis in 480 patients (10.6%) with a median onset of 105 days following ADC initiation. Conclusions: In this large, multi-center real-world cohort, ADC treatment was associated with substantial rates of neurologic, hematologic, and cardiac toxicities. The frequent use of concomitant anticancer treatments and observed transitions between ADCs underscore the complexity of real-world exposure and highlight the need for proactive toxicity monitoring and optimized safety management strategies in routine oncology practice.
Barriers and variability in lymphedema therapy for head and neck cancer survivors: Secondary analysis from a randomized trial.
6108 Background: Secondary lymphedema is a significant underrecognized sequela of head and neck cancer (HNC) and its treatments. Lymphedema may impact external structures (head, face, neck) and internal structures (larynx, pharynx), leading to functional impairments impacting breathing, speaking and swallowing resulting in disability, and reduced quality of life. Although therapist guided lymphedema treatment (TGLT) is effective, timely access is frequently limited by financial constraints, geographic barriers, systemic inefficiencies, and shortages of trained therapists. This study evaluates accessibility, implementation, and barriers to TGLT in HNC survivors. Methods: This prospective cohort study was nested within a multi-site randomized trial comparing usual care to an advanced pneumatic compression device (APCD). Eligible participants (N=117) were HNC survivors with lymphedema and at least one lymphedema-associated symptom rated ≥4/10. Therapy notes and patient data were abstracted to assess referral patterns, therapy timelines, lymphedema treatment characteristics, documented therapeutic goals, and reported barriers. Descriptive statistics were obtained to depict trends in therapy initiation, implementation, and barriers. Results: Of 117 participants referred for therapy, 77 (66%) were evaluated by a therapist. Of these, 11 failed to return for a second visit (56%). Median time from referral to evaluation was 17 days. Median time from evaluation to last recorded visit was 72.5 days (median 10 visits). Many patients experienced protracted wait times (Figure 1) and treatment breaks. Therapy delivery varied substantially; By last documented visit, recommendations included home manual lymphatic drainage (82%), compression garments (65%), APCD (33%), and written self-care instructions (26%). 28% achieved all therapy goals. Documentation inconsistencies and gaps in provider communication hindered effective therapy implementation. Barriers included geographic distance, financial constraints, and therapist shortages. Conclusions: Significant variability, limited care access, and delays in TGLT exist for HNC survivors. Standardized protocols, telemedicine, and adjunctive technologies such as APCDs may improve accessibility, adherence, and outcomes. Future studies should focus on optimizing care models including self-care and reducing disparities in therapy delivery. Clinical trial information: NCT04797390 . Timeframe of therapy implementation in days. Provider Referral to Therapy Evaluation Therapy Evaluation to Second Visit Provider Referral to Second Visit Therapy Evaluation to Last Visit Average 23.7 9.0 32.7 80.0 Standard deviation 21.9 6.8 23.3 44.9 Median 17.0 7.0 27.0 72.5 Minimum 0.0 1.0 1.0 7.0 Maximum 93.0 31.0 108.0 175.0 25th percentile 8.0 4.0 16.3 48.0 75th percentile 31.8 14.0 44.5 103.5
Epidemiological trends and burden of esophageal cancer in the United States, 1990–2023: A retrospective analysis with machine learning projections to 2050.
e16058 Background: Esophageal cancer remains a significant cause of cancer-related mortality in the United States, with risk factors including smoking, alcohol, obesity, and gastroesophageal reflux disease contributing to its burden. This study analyzed age-standardized rates (ASRs) of DALYs, deaths, incidence, and prevalence from 1990 to 2023 using IHME GBD 2023 data, evaluated trends through estimated annual percentage change (EAPC), and projected future burden to 2050 employing ARIMA time-series models. Methods: Age-standardized rates per 100,000 population were retrieved from the Global Burden of Disease 2023 database for the United States, stratified by sex (Both, Female, Male). Historical trends (1990–2023) were assessed via EAPC derived from linear regression on log-transformed ASRs. Future projections (2024–2050) were generated using ARIMA models fitted to historical data, yielding point forecasts and 95% prediction intervals (PI). Results: From 1990 to 2023, age-standardized DALYs (Both sexes) decreased from 96.08 (95% UI: 88.99–103.15) to 84.02 (95% UI: 76.56–91.25), with an EAPC of -0.49% (95% CI: -0.61 to -0.36); females experienced a steeper decline (EAPC -0.84%, 95% CI: -0.91 to -0.77) than males (EAPC -0.52%, 95% CI: -0.67 to -0.37). Age-standardized death rates fell from 3.76 to 3.51 (EAPC -0.28%, 95% CI: -0.41 to -0.14), again with greater reductions in females (EAPC -0.78%) than males (EAPC -0.30%). Incidence declined modestly from 4.32 to 4.15 (EAPC -0.23%, 95% CI: -0.39 to -0.07), while prevalence showed near-stability overall (EAPC -0.08%, 95% CI: -0.29 to 0.13), reflecting improved survival offsetting some incidence reductions. ARIMA forecasts indicate continued gradual declines in age-standardized DALYs (Both: from 83.13 in 2024 to 59.97 by 2050), deaths (approaching ~2.56 by 2050), and incidence (to ~3.16 by 2050), while prevalence remains relatively stable or slowly erodes, influenced by demographic aging and modest therapeutic progress. Conclusions: Age-standardized burden of esophageal cancer in the US declined modestly from 1990–2023 across key metrics, with more pronounced improvements in females and limited progress in males. Projections to 2050 suggest ongoing reductions in DALYs, mortality, and incidence, though absolute case numbers may persist due to population growth and aging, highlighting the need for enhanced prevention, screening, and treatment strategies. Measure Sex EAPC Lower 95%CI Upper 95%CI DALYs Both -0.49 -0.61 -0.36 DALYs Female -0.84 -0.91 -0.77 DALYs Male -0.52 -0.67 -0.37 Deaths Both -0.28 -0.41 -0.14 Deaths Female -0.78 -0.87 -0.7 Deaths Male -0.3 -0.46 -0.14 Incidence Both -0.23 -0.39 -0.07 Incidence Female -0.62 -0.73 -0.5 Incidence Male -0.25 -0.44 -0.06 Prevalence Both -0.08 -0.29 0.13 Prevalence Female -0.31 -0.46 -0.15 Prevalence Male -0.09 -0.33 0.14
Age as a determinant of systemic therapy initiation in advanced colorectal cancer: Experience from an urban safety-net hospital.
e13763 Background: Access is often cited as the primary hurdle in safety-net oncology, yet geriatric factors may drive treatment attrition. In urban settings with high insurance coverage but significant clinical complexity, the independent impact of age on therapy initiation remains poorly defined. We evaluated whether age dictates systemic therapy initiation for advanced colorectal cancer (CRC) in a predominantly minority safety-net population. Methods: We conducted a retrospective analysis of the Newark Beth Israel Medical Center cancer registry, identifying patients diagnosed with stage III–IV epithelial CRC between 2023 and 2024. The primary outcome was initiation of systemic therapy (chemotherapy and/or immunotherapy). Associations between treatment initiation and age, disease stage, insurance status, and race/ethnicity were evaluated using Fisher’s exact tests. Multivariable logistic regression was performed, modeling age as a continuous variable and adjusting for disease stage. Results: Among 44 patients included, 47.7% had stage III disease and 52.3% had stage IV disease. The cohort was predominantly Non-Hispanic Black (76.1%). Overall, 63.6% of patients initiated systemic therapy. Insurance status was not statistically associated with treatment initiation; notably, all untreated patients were insured, primarily through Medicare or Medicaid. Disease stage similarly showed no significant association with therapy receipt. In contrast, treatment initiation declined substantially with increasing age, from 71.4% among patients younger than 65 years to 28.6% among those aged 65 years or older (p = 0.003). On multivariable analysis, each additional year of age was associated with an 8% decrease in the odds of systemic therapy initiation (OR 0.92; 95% CI 0.86–0.97; p = 0.004). Documented medical contraindications and treatment refusal were uncommon contributors to non-initiation. Conclusions: In this safety-net cohort, increasing age was strongly associated with non-initiation of therapy despite insurance and advanced stage. Findings suggest care delivery decision-making, rather than access, may drive these disparities. Integrating structured geriatric assessments may help distinguish physiologic vulnerability from chronologic age, supporting individualized care in safety-net settings.
Validating a single-item screener for low digital health literacy among surgical oncology patients.
1634 Background: Digital health literacy (DHL; the ability to find and understand health information using electronic media) may affect surgical oncology patients’ ability to navigate patient education and discharge coordination activities that rely on technology. Screening for low DHL can identify patients who may benefit from alternate modalities or additional support. In our prior work, a single item from the validated electronic Health Literacy Scale (eHEALS) had strong sensitivity and specificity for identifying low DHL in the outpatient setting. In this cross sectional, secondary analysis, we explored which sociodemographic and clinical factors were related to low DHL and tested whether the single-item screener could identify patients with low DHL in the surgical oncology setting. Methods: Surgical oncology patients were recruited during their post-operative hospitalization for a parent study on health literacy and clinical outcomes. The 8-item eHEALS assessed DHL; total scores ≤20 indicate low DHL. Chi-squared, Fisher’s exact, or Mann-Whitney tests were used to examine whether DHL varied by patients’ sociodemographic (age, sex, race/ethnicity, education, marital status, general health literacy) or clinical characteristics (cancer type, ECOG performance status, comorbidities). Receiver operating characteristic (ROC) curve analysis assessed sensitivity, specificity, and accuracy of eHEALs item 4 ("I know where to find helpful health resources on the Internet") to identify low DHL. Results: Participants (N=224) were primarily non-Hispanic White (87%), older (median=68, IQR 61-75 yrs), married (69%), men (59%) with gastrointestinal cancer (60%) who completed at least some college education (76%). On the 8-item eHEALS, 23 patients (10.3%) reported low DHL. Patients with lower general health literacy (p<0.001), lower education level (p=0.007), and unpartnered marital status (X 2 = 4.359, p=0.039) were more likely to have low DHL. Other factors were not associated with DHL (p-values>0.299). Older patients were marginally more likely to report low DHL than younger patients (U=2847, p=0.069). In ROC curve analysis, eHEALS item 4 strongly distinguished low DHL vs. high DHL (AUC=0.989; 95% CI 0.977-0.997). At the optimal threshold (item scores <3, on a 1-5 Likert scale), item 4 predicted low DHL with an accuracy of 96.9%, sensitivity of 97.0%, and specificity of 95.7%. Conclusions: These data suggest a single-item screener (eHEALS item 4) can accurately identify patients with low DHL in the surgical oncology setting, adding support for its ability to detect low DHL in patients with cancer. Among surgical oncology patients, those with lower education, lower general health literacy, and older age may be more likely to experience lower DHL. Future prospective studies with larger samples are warranted to assess utility, acceptability, and feasibility of the screener in clinical practice.
Combining HC-7366 with belzutifan in patients with renal cell carcinoma to alter tumor and microenvironment: Pharmacokinetic and pharmacodynamic (PK/PD) analysis of a phase 1b study.
4535 Background: Clear cell renal cell carcinoma (ccRCC), characterized by loss of von Hippel-Lindau (VHL) tumor suppressor function, and constitutive stabilization of hypoxia-inducible factor (HIF) proteins results in activation of genes promoting angiogenesis, metabolic reprogramming including altered lipid metabolism and glycolysis, cell proliferation, and immunosuppressive remodeling of the tumor microenvironment. HC-7366 is a novel, selective GCN2 kinase activator that regulates metabolic stress via the ATF4–driven integrated stress response. Preclinically, GCN2 hyperactivation with HC-7366 enhances belzutifan (BEL) activity, broadly impairing stress adaptation, disrupting tumor metabolism, decreasing HIF expression, inhibiting the cell cycle, and remodeling the tumor immune microenvironment. Methods: In this phase 1b study (NCT06234605), 69 patients with advanced ccRCC received HC-7366 monotherapy (60 mg QD; n=16) or HC-7366 (20 mg, n=7; 40 mg, n=22; 60 mg, n=24) plus BEL (120 mg QD). Blood samples for soluble biomarkers and paired biopsies for IHC were collected per IRB-approved guidelines. Results: Overall, PK analysis (N=69) demonstrated steady state free exposure of HC-7366 at 40-60 mg doses (Cmax = 5.8 ng/mL, AUC = 75 h*ng/mL) that were consistent with exposures providing maximal BEL combination benefit preclinically. Compared with screening biopsies, all on-treatment biopsies at week 3 (8/8) showed induction of the ATF4 pathway biomarker ASNS (asparagine synthetase). Baseline HIF expression analysis by IHC from 52 patients demonstrated that 33 patients (63%) express mid to high levels of HIF1 and HIF2. HIF1α, but not HIF2α, was reduced consistently with treatment across all cohorts (7/8, 66-98% reduction). Reduced cell cycle biomarkers, including pRB and Ki67 (4/4), and increased frequency of CD8 + PD1 + TCF1 + Lag3 - Tim3 - T-cells (3/3), suggesting ICI responsiveness, were observed in the 40-60 mg combination cohorts. Systemic changes were also observed in serum, including deep and sustained inhibition of EPO, decreases in proangiogenic cytokines like VEGF-A and PDGF-BB, and changes in adipokines that counter RCC progression (Table 1). Low baseline serum levels of KIM-1 predicted response to the combination (p=0.005). Conclusions: Early clinical findings suggest HC-7366 + BEL is associated with modulation of angiogenic and immune-related pathways in ccRCC, providing a rationale for the combination with ICIs and/or VEGFR-TKIs. Clinical trial information: NCT06234605 . Avg max change with treatment. Biomarker 60 mg mono 20 mg combo 40 mg combo 60 mg combo EPO (week 2) -43% -82% -81% -84% Chemerin (week 2) -34% -16% -36% -28% Adiponectin (week 5) +64% +35% +46% +36% VEGF-A (week 9) -53% -42% -28% -37% PDGF-BB (week 9) -30% -20% -54% -63%
Light‐Induced Chiral Aldehyde/Palladium Catalysis‐Enabled Asymmetric Allylic C─H Alkylation of Alkenes With NH <sub>2</sub> ‐Unprotected Amino Acid Derivatives
ABSTRACT The catalytic asymmetric allylic C–H alkylation of alkenes with the α‐carbon of readily available amino acid derivatives represents an ideal strategy for constructing chiral nonproteinogenic α,α‐disubstituted amino acids. However, such synthetic methodologies remain unexplored. Herein, we report a light‐induced, chiral aldehyde/palladium catalysis‐enabled direct allylic C–H alkylation of allyl arenes and 1,4‐enynes using NH 2 ‐unprotected amino acid esters. The results demonstrate that competing allylic C–H amination is completely suppressed, and the desired alkylation products—bearing either allyl or conjugated enyne moieties—are obtained in 32%–93% yields with 80%–98% ee values. Mechanistic studies reveal that enantiocontrol is achieved through the cooperative action of the chiral aldehyde and the chiral ligand, and the latter primarily dictates the absolute configuration of the product by forming noncovalent C–H···π and C–H···O interactions with the chiral aldehyde‐involved Zn complex.
Amyloid‐Like Nanocoatings for Enhanced Hemoperfusion Materials
ABSTRACT Hemoperfusion, a therapeutic technique in which blood is circulated through extracorporeal adsorbents to remove toxins, faces the challenge of simultaneously enhancing the adsorption performance and hemocompatibility of hemoperfusion materials (HPMs) through a facile and eco‐friendly surface engineering strategy. Herein, a one‐step amyloid‐mediated surface modification method is proposed to encapsulate HPMs by immersing them in a phase‐transitioned bovine serum albumin (PTB) aqueous solution. The resultant amyloid‐like PTB nanocoating modified activated carbon exhibited a nearly four‐fold increase in the adsorption capacity for urea and creatinine, as well as significantly enhanced adsorption toward other harmful substances, including heavy metal chromium ion, drug norfloxacin, medium‐molecule toxin bilirubin, and large‐molecule toxin interleukin‐6. Additionally, the hemocompatibility of activated carbon is substantially improved by reducing carbon debris formation, minimizing damage to blood cells, and effectively alleviating non‐specific adsorption of plasma proteins while resisting platelet adhesion. The superior blood purification performance was validated in vivo using multiple animal models of chronic kidney disease. Notably, this strategy is broadly applicable to various HPMs, such as polymeric resins and emerging materials such as carbon nanotubes and metal‐organic frameworks, offering an effective and highly general surface engineering approach to enhance the performance of various blood purification materials with significant clinical implications.