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2025’s FDA approvals by regulatory designations

Single‐Molecule All‐In‐One (SMALL) Dendritic Dots for Precise Cancer Theranostics

ABSTRACT Multifunctional nanoparticles with diverse cargos have been extensively developed for efficient cancer theranostics. However, the requirement of additional components would result in stochastic functionalization, interfering with the precise structure and desired characteristics. Thus, it is requisite and challenging to develop multifunctional nanoparticles with a single component. Herein, we report a universal, modular and scalable design approach for constructing a type of single‐molecule all‐in‐one (SMALL) dendritic dots (DDs) with well‐defined functional architectures for customizable theranostics. These SMALL DDs are prepared through dendrimer‐based divergent synthesis by orthogonal protection, selective deprotection, and precise conjugation. To demonstrate the feasibility of the strategy, we synthesized a type of perylenediimide (PDI)‐cored and camptothecin‐loaded polylysine dendrimer‐based SMALL DDs. These DDs possess precise structure, tunable drug loading, well‐defined particle size, and bright and stable fluorescence. The SMALL DDs exhibit long blood circulation, superior tumor accumulation, and tumor‐associated enzyme‐responsive drug release and generate potent antitumor activity in mice bearing hepatocellular carcinoma. The SMALL DDs integrate imaging probes, drug molecules, and targeting and responsive ligands into a single molecule, which provides a strategy to solve the dilemma of multifunctionality and structural precision and is promising for cancer theranostics.

Arch Shaped Triboelectric Nanogenerator for Wave Energy Harvesting and Corrosion Protection

ABSTRACT As a renewable energy source, wave energy exploitation reduces fossil energy pollution and aids carbon neutrality. Traditional electromagnetic generators (EMGs) have low low‐frequency conversion efficiency, limiting large‐scale application. Triboelectric nanogenerators (TENGs), invented in 2012, offer a new way for wave energy harvesting with advantages of wide material selection, low‐frequency adaptability, light weight and low cost, but are restricted by marine corrosion and inefficient low‐frequency capture. This work designed an arch‐structured TENG (Arch‐TENG) that captures wave energy via bending. Compared with CS‐TENG, its charge transfer increases by over 450%, with a charge output density of 12.7 nC cm 2 at 0.5 Hz and stable performance after 26 h tests. The array‐integrated device capable of large‐scale wave energy harvesting is designed based on the Arch‐TENG. It was verified that this device can not only stably power low‐power electronic devices but also be used for cathodic protection tests of carbon steel Q235 in seawater, which will provide more practical applications of TENG in marine environments.

Serum IgG: A novel biomarker for efficacy and prognosis in metastatic clear cell renal cell carcinoma patients receiving first-line immunotherapy combined with tyrosine kinase inhibitors.

445 Background: The first-line use of immunotherapy in combination with tyrosine kinase inhibitors (IO-TKIs) significantly improves the overall prognosis of patients with metastatic clear cell renal cell carcinoma (mccRCC). Nevertheless, clinically applicable biomarkers for predicting the prognosis and efficacy of first-line IO-TKIs therapy remain elusive. Methods: We retrospectively evaluated 121 mccRCC patients treated with first-line IO-TKIs to assess the prognostic value of serum immunoglobulin G (IgG), neutrophil-to-lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), their 3-month dynamic changes, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group. The Kaplan-Meier survival curves were drawn to show the differences in progression-free survival (PFS) and overall survival (OS) among various clinical subgroups. Univariate and multivariate COX analyses were used to identify the independent prognostic factors. The time-dependent ROC curves were plotted to compare the ability of each model to predict specific PFS and OS time points. Results: At a median follow-up of 31 months for the cohort (median age 60 years), the objective response rate was 63.64%. The median PFS was 18 months; however, the median OS was not reached. Baseline IgG levels were comparable across the partial response (PR)/complete response (CR), stable disease (SD), and progressive disease (PD) groups (P = 0.160). Following 3 months of treatment, PR/CR group experienced a significant decline in IgG (P < 0.001), SD group showed stable levels (P = 0.235), and PD group demonstrated a significant elevation (P < 0.001). Elevated serum IgG after 3 months of treatment was associated with worse PFS (HR = 3.92, P < 0.001) and OS (HR = 3.96, P < 0.001). High IMDC score, high baseline mGPS, and baseline NLR (≥3) predicted poorer PFS and OS. Multivariate COX analysis showed that IgG alteration and baseline mGPS were independent prognostic factors for PFS and OS in mccRCC patients receiving first-line IO-TKIs. At 16 months of PFS, IgG alteration (AUC = 0.795) exhibited superior performance compared to other predictors (baseline mGPS: AUC = 0.679, baseline NLR: AUC = 0.694, IMDC: AUC = 0.651). At 50 months of OS, IgG alteration (AUC = 0.680) demonstrated non-inferior predictive capability compared to other indicators (baseline mGPS: AUC = 0.747, baseline NLR: AUC = 0.673, IMDC: AUC = 0.574). Conclusions: Serum IgG alterations emerge as a superior independent prognostic biomarker in mccRCC patients receiving first-line IO-TKIs.

Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) N-of-1 Precision Oncology Study: Molecular Profiling to Match Individually Dosed, Personalized Drug Combinations

PURPOSE Malignancies have complex and distinct molecular profiles that may not segregate by tumor type. However, most precision oncology treatments are matched to a single biomarker. We aimed to optimize therapy for advanced cancers using individually dosed drug regimens customized to cotarget multiple molecular alterations. METHODS Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT; NCT02534675 ) is a prospective, investigator-initiated, multidepartment/pan-cancer trial for aggressive advanced/metastatic malignancies. Patients had tissue and/or blood next-generation sequencing (NGS; Foundation Medicine). A molecular tumor board made suggestions. Degree of biomarker matching to drugs given was calculated by a matching score (MS; broadly, number of pathogenic alterations targeted divided by total pathogenic alterations). RESULTS Overall, 210 evaluable patients (n = 456 consented) received ≥1 US Food and Drug Administration–approved drug (mostly off label) after NGS. Median number of pathogenic alterations/tumor was five (range, 0-20); approximately 95% of patients had unique molecular landscapes. Consistent with I-PREDICT's objective to optimize/tailor treatment for each patient, we administered 157 different regimens (including 103 personalized combinations without established safety/dosing data). For previously unstudied combinations, starting doses were reduced and titrated to tolerance (intrapatient dose-finding); only 6.5% experienced Grade 3/4 drug-related toxicities ( v 15.5% of those receiving established regimens). Higher disease control rate (stable disease ≥6 months/objective response), and longer progression-free survival and overall survival correlated significantly/independently/linearly with greater degrees of drug matching to alterations (higher MS), but did not vary by drug number or dosages. CONCLUSION The I-PREDICT strategy of maximizing personalized biomarker matching with individually dosed customized drug combinations enabled safe and active N-of-1 matched treatment, including regimens previously unstudied in Phase I trials. I-PREDICT represents a blueprint for a new personalized precision oncology paradigm, which merits validation via additional prospective trials.

Detection of bone metastases in men with low PSA biochemical recurrence of prostate cancer with ¹⁸ F-flotufolastat PET/CT: A post-hoc analysis from the phase 3 SPOTLIGHT study.

31 Background: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has become the mainstay of prostate cancer imaging. The SPOTLIGHT study (NCT04186845) assessed the diagnostic performance of PSMA-targeted PET radiopharmaceutical, 18 F-flotufolastat, in men with suspected biochemical recurrence (BCR) of prostate cancer and showed it to have high detection rates even among patients with low prostate-specific antigen (PSA) values. Here, we present the results of a post-hoc analysis of SPOTLIGHT that aimed to determine the 18 F-flotufolastat verified detection rate for bone metastases in patients with a PSA level <0.5 ng/mL. Methods: Men with suspected BCR of prostate cancer underwent PET/CT 50–70 min after IV administration of 18 F-flotufolastat (296 MBq ± 20%). Three blinded central readers interpreted the 18 F-flotufolastat scans, with results presented as a majority read. Standard of truth (SoT) was established for each patient using histopathology or confirmatory conventional imaging (including CT, MRI, 99m Tc bone scan, 18 F-NaF PET/CT or 18 F-fluciclovine PET/CT). For the present analysis, all patients who had an evaluable scan were included if they had a baseline PSA level <0.5 ng/mL. Results: In total, data from 121 patients with an evaluable scan and PSA level <0.5 ng/mL were evaluated. Of these, 105 patients had sufficient data to determine a SoT (median PSA, 0.30 ng/mL). The patient-level 18 F-flotufolastat DR for this cohort of patients with low PSA was 64% (77/121) by majority read, with a DR of 21% (25/121) in extrapelvic lesions. Bone lesions were detected in 15% (18/121) of the patients. SoT verification of these bone lesions was predominantly by conventional imaging, with histopathology available for just 2/18 (11%) bone lesions. In total, 10/18 bone lesions were confirmed as true positive, yielding a verified detection rate in bone of 9.5% (10/105). Conclusions: This post-hoc analysis of a prospective Phase 3 clinical study demonstrates that 18 F-flotufolastat has a clinically meaningful detection rate for bone metastases in this low PSA population, identifying a true positive bone metastasis in at least one in ten patients (as bone biopsy is not often clinically indicated to allow for histopathology as SoT) with a PSA level <0.5 ng/mL. Clinical trial information: NCT04186845 .

PD1 blockers work best when used in the morning, suggests cancer chronotherapy trial

Reconfigurable Non‐Hermitian Topological Photonic Lattice via Reversible Quantum Dot Waveguides

ABSTRACT Non‐Hermitian systems extend conventional Hermitian quantum frameworks by incorporating factors like gain and loss, giving rise to novel phenomena such as exceptional points and the non‐Hermitian skin effect. Building on these foundations, non‐Hermitian topological photonics merges them with topological band theory, enabling unprecedented control of light. The tunability of non‐Hermitian parameters allows for on‐demand reconfigurable topological devices within a fixed platform, thereby bridging the gap between exotic non‐Hermitian topological phenomena and practical applications. Here, we present a reconfigurable non‐Hermitian topological photonic lattice with tunable loss, realized on a novel platform of reversible perovskite quantum dot waveguide arrays. By strategically modulating the waveguide loss, we experimentally demonstrate a non‐Hermitian‐induced topological phase transition and the emergence of interface states. The reversible and tunable characteristics of perovskite quantum dot waveguides establish a versatile platform for exploring topological states and advancing on‐chip photonic applications.

Probing Cellular Activity Via Charge‐Sensitive Quantum Nanoprobes

ABSTRACT Nitrogen‐vacancy (NV) based quantum sensors hold great potential for real‐time single‐cell sensing with far‐reaching applications in fundamental biology and medical diagnostics. Although highly sensitive, the mapping of quantum measurements onto cellular physiological states has remained an exceptional challenge. Here, we introduce a novel quantum sensing modality capable of detecting changes in cellular activity. Our approach is based on the detection of environment‐induced charge depletion within an individual particle that, owing to a previously unaccounted transverse dipole term, induces systematic shifts in the zero‐field splitting (ZFS). Importantly, these charge‐induced shifts serve as a reliable indicator for lipopolysaccharide (LPS)‐mediated inflammatory response in macrophages. Furthermore, we demonstrate that surface modification of our diamond nanoprobes effectively suppresses these environment‐induced ZFS shifts, providing an important tool for differentiating electrostatic shifts caused by the environment from other unrelated effects, such as temperature variations. Notably, this surface modification also leads to significant reductions in particle‐induced toxicity and inflammation. Our findings shed light on systematic drifts and sensitivity limits of NV spectroscopy in a biological environment with ramifications for the critical discussion surrounding single‐cell thermogenesis. Notably, this work establishes the foundation for a novel sensing modality capable of probing complex cellular processes through straightforward physical measurements.

Trends in renal cell carcinoma mortality associated with tobacco use in U.S. adults aged ≥45 years, 1999–2023: A population-based CDC WONDER analysis.

434 Background: Renal cell carcinoma (RCC) is one of the common malignancies in the United States. Tobacco exposure is an established risk factor for renal cell carcinoma (RCC). Despite declining smoking prevalence in the United States, its impact on RCC mortality remains unclear. Methods: Using CDC WONDER multiple-cause-of-death data (1999–2023), we identified deaths in adults aged ≥45 years with malignant neoplasm of the kidney (C64) and tobacco use disorder (F17). Age-adjusted mortality rates (AAMR, per 100,000) were analyzed by sex, age, and Census regions. Temporal trends were assessed using Joinpoint regression to estimate average annual percent change (AAPC). Results: From 1999 to 2023, a total of 27,893 deaths were attributed to RCC and tobacco smoking among U.S. adults aged ≥45 years. The overall average AAMR was 0.84, rising from 0.06 in 1999 to 1.19 in 2023 (AAPC: 16.3%, p = 0.001). The most pronounced significant increase in AAMR occurred between 1999–2004 (APC: 72.3%, p = 0.001), followed by a continued rise through 2012 (APC: 10.4%, p = 0.001), and a non-significant increase thereafter (APC: 1%, p = 0.19). Adult males had a higher average AAMR than females (1.41 vs 0.40). From 1999 to 2023, AAMR increased significantly in both sexes, rising from 0.1 to 2.11 in males (AAPC: 13.9%, p = 0.001) and from 0.04 to 0.61 in females (AAPC: 13.6%, p = 0.001). Older adults (≥65 years) demonstrated a higher average AAMR (1.69) compared to middle-aged adults (45–64 years; 0.36). The greatest increase was seen in older adults, with AAMR rising from 0.1 to 2.59 (AAPC: 14.4%, p = 0.001). A similar significant increase was observed in middle-aged adults, from 0.04 to 0.48 (AAPC: 11.8%, p = 0.001). Across census regions, the Midwest recorded the highest average AAMR (1.23), followed by the South (0.8) and the West (0.62). The Midwest also showed the steepest increase, from 0.04 to 1.97 (AAPC: 17.4%, p = 0.001), followed by the South (0.07 to 1.25, AAPC: 14.4%, p = 0.001) and the West (0.07 to 0.85, AAPC: 14.1%, p = 0.001). Conclusions: Rising tobacco-related RCC mortality, particularly among older adults, males, and Midwestern populations, highlights persistent disparities and supports the need for strengthened prevention and early-detection strategies.

Randomized Parallel-Group Phase II Study (NEOTERIC) of Atezolizumab With or Without Tiragolumab After Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

PURPOSE Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for patients with locally advanced rectal cancer (LARC); however, pathologic complete response (pCR) rates and long-term outcomes remain suboptimal. This study evaluated the safety and efficacy of atezolizumab (Atezo) with or without tiragolumab (Tira) after nCRT in patients with LARC. METHODS This randomized, parallel-group, phase II study included a safety run-in and a subsequent randomized phase. Eligible patients (cT3N+M0 or cT4NanyM0) received long-course nCRT (45-50.4 Gy in 25-28 fractions with concurrent capecitabine), followed by three 21-day cycles of Atezo (1,200 mg once on day 1 of each cycle), either combined with Tira (600 mg; Atezo + Tira arm) or alone (Atezo arm). Radical surgery was performed 2 weeks after final dose. The primary end point was pCR rate. Secondary end points included 1-year event-free survival (EFS) rate and safety. Outcomes were compared with historical controls. RESULTS At data cutoff (January 6, 2025), three patients were enrolled in safety run-in and received Atezo + Tira. In randomized phase, 55 patients were assigned 1:1 to Atezo + Tira arm (n = 28) or Atezo arm (n = 27). pCR rate was 35.7% (95% CI, 18.6 to 55.9; v historical control [15%] P = .002) in Atezo + Tira arm and 22.2% (95% CI, 8.6 to 42.3; v historical control [15%] P = .293) in Atezo arm. After a median follow-up of 21.55 months (range, 20.67-22.24), 1-year EFS rates were 96.3% (95% CI, 76.5 to 99.5) in Atezo + Tira arm and 92.1% (95% CI, 72.1 to 98.0) in Atezo arm. Grade 3 to 4 treatment-related adverse events occurred in 31.0% and 26.9%. Grade 3 to 4 AEs related to Atezo or Tira were 10.3% and 11.5%, respectively. No treatment-emergent deaths were reported. CONCLUSION In patients with LARC, Atezo + Tira after nCRT statistically improved the pCR rate compared with historical controls, with an acceptable safety profile.

EGFR, HER2 alterations in advanced urothelial carcinoma (aUC): A retrospective analysis on survival outcomes.

787 Background: EGFR alterations (EGFR-alt) and HER2 alterations (ERBB2-alt) are each seen in approximately 4% of advanced urothelial carcinomas (aUC). Given the success of targeted therapies in other solid tumor malignancies such as breast and lung cancers, proper prognostication and targeted therapy development is critical for HER2 and EGFR mutations in aUC. Methods: Between 1/1/2017 and 5/1/2024, aUC patients were identified from US cancer clinics in Flatiron Health’s de-identified electronic health record database. Baseline characteristics, treatment history, and clinical outcomes were abstracted on patients with EGFR-alt or ERBB2-alt (single-nucleotide variant (SNV), copy number variant (CNV), or rearrangement) on Next Generation Sequencing. Chi-square and t-tests were used for used for univariate analysis. Progression free survival (PFS) and overall survival (OS) of EGFR-alt and ERBB2-alt versus wild type (WT) patients were estimated via Kaplan Meier curves and compared via log-rank analysis and Cox regression. Results: 1110 patients met inclusion criteria, of which 786 were wild-type (WT), 238 had ERBB2 alterations and 80 had EGFR alterations. 51 (5%) had single nucleotide variants (SNV) in EGFR and 155 (14%) in ERBB2. 4 ( < 1%) had rearrangements in EGFR and 19 (2%) in ERBB2. 35 had (4%) copy number variants (CNV) of EGFR and 114 (10%) CNV of ERBB2. Distribution of men vs. women was comparable in EGFR/ERBB2 SNVs (p = 0.35), rearrangements (p = 0.29), and CNV (p = 0.29). Race was also comparable (p = 0.98, p = 0.97, p = 0.45 respectively), as was age > 65 years vs < 65 (p = 0.06, p = 0.43, p = 0.67, respectively). There was no difference in cisplatin, carboplatin, immunotherapy use for SNV (p = 0.24), rearrangement (p = 0.52), or CNV (p = 0.36). Patients with ERBB2-alt had longer PFS compared to WT patients (median 9.3 months vs 6.3 months; p = 0.005), and longer OS than WT patients (median 22.8 vs 16.5, p = 0.04). PFS for ERBB2 SNV was longer than WT on multivariate analysis (6.6 months vs. 5.0 months, p = 0.02). For EGFR alterations, PFS was comparable to WT (4.8 vs 5.0; p = 0.259), and OS was not significantly improved vs WT (15.2 vs 14.0, p = 0.737). There was no association between EGFR and ERBB2 rearrangements with PFS (p = 0.4) or OS (p = 0.3). There was no association between EGFR and ERBB2 CNV with PFS (p = 1) or OS (p = 0.9). Conclusions: In aUC patients, ERBB2-alt were associated with longer PFS and OS compared to WT or EGFR-alt patients, particularly with ERBB2 SNV alterations.

GSK pays US$2 billion for prophylactic food allergen antibody

Prussian Blue Analog as a Functional Additive for Restoring Sulfide Solid Electrolytes: Enhancing Moisture Stability in All‐Solid‐State Batteries (Adv. Mater. 13/2026)

Puncture‐Needle‐Integrated Optical Fibers and NIR‐II‐Activated Thermosensitive Hydrogels for Deep‐Seated Tumor Therapy

ABSTRACT Deep‐seated tumors are difficult to treat because of their location, conventional treatment resistance, and limited light penetration during photothermal therapy (PTT). Interstitial PTT with “inside‐out” laser irradiation using optical fibers (OFs) offers a promising solution. This study proposes a drug‐device integrated platform assisted by a puncture needle combining stimuli‐responsive hydrogels with a spherical‐tip polymer OF ( SPOF ) to overcome dual challenges: Inadequate photothermal agent retention and insufficient optical penetration. The injectable thermosensitive hydrogel ( SW8@Gel ), composed of Pluronic F127 and aza‐boron‐dipyrromethene‐derived SW8 nanoparticles, rapidly undergoes sol–gel transition at 38°C, facilitating localized and sustained delivery of the photothermal agent. The flexible low‐bending‐loss SPOF emits 360° divergent near‐infrared II (1064 nm) light from its spherical tip, allowing single‐fiber illumination of deep‐seated tumors (penetration >10 cm) in complex biological environments. Integrating these components enables depth‐adaptive tumor ablation. Compared to other methods, the SPOF / SW8@Gel combination demonstrates the lowest frequency and shortest duration for PTT of deep‐seated tumors and achieves superior efficacy, with a 90% tumor regression rate in mice models and no off‐target damage due to enhanced heating uniformity and reduced systemic toxicity. This platform offers a transformative clinically viable solution for precise ablation of deep malignancies, bridging advanced photonics and targeted oncotherapy.

Clinical and social determinants of definitive surgical management in bladder cancer: A two-decade population-based analysis from the United States.

654 Background: Surgical management of bladder cancer ranges from bladder-preserving approaches to radical cystectomy. We examined factors associated with receipt of definitive bladder surgery using a large population-based cohort. Methods: We analyzed 386,304 bladder cancer patients from the SEER database (2000-2022). The primary outcome was receipt of definitive bladder surgery (excisional biopsy, partial cystectomy, or radical cystectomy) versus no surgery/local ablation only. Multivariable logistic regression was used to identify predictors adjusting for demographic, clinical, and socioeconomic factors. Results: Among 386,304 patients, 76.0% were male and 24.0% female. Median age was 72 years (IQR 63-78). The cohort was 82.6% Non-Hispanic White, 6.6% Hispanic, 5.4% Non-Hispanic Black, 4.3% Non-Hispanic Asian/Pacific Islander, and 0.4% Non-Hispanic American Indian/Alaska Native. By stage: 41.2% had carcinoma in situ, 30.3% localized disease, 5.9% regional disease, and 4.1% distant metastases. Most patients (58.2%) were married at diagnosis. Surgical Patterns: Overall, 66.6% underwent excisional biopsy (code 27), 10.8% had electrocautery/fulguration, 8.4% had no surgery, 3.4% underwent partial cystectomy (code 71), and 2.6% had radical cystectomy (code 61). Only 7.6% underwent lymph node dissection (6.8% with ≥4 nodes removed). Multivariable Analysis: In adjusted analysis (n=368,219 with complete data), factors associated with definitive surgery included: Increased likelihood: Male sex (OR 1.06, 95% CI: 1.04-1.08, p<0.001), higher income ($120,000+ vs <$40,000: OR 1.51, 95% CI: 1.39-1.64, p<0.001), extensive lymph node dissection (≥4 nodes removed: OR 20.16, 95% CI: 16.32-24.90, p<0.001). Decreased likelihood: Non-Hispanic White race (vs Hispanic: OR 0.94, 95% CI: 0.91-0.97, p<0.001), distant metastases (OR 0.37, 95% CI: 0.35-0.39, p<0.001), regional disease (OR 0.50, 95% CI: 0.48-0.54, p<0.001), unknown stage (OR 0.10, 95% CI: 0.09-0.11, p<0.001), unmarried status (single: OR 0.60, 95% CI: 0.58-0.62, p<0.001), increasing age (OR 0.999 per year, p=0.018). Conclusions: Definitive bladder surgery patterns reveal significant disparities. Male patients and those with higher socioeconomic status were more likely to receive surgical treatment, while racial minorities (specifically Hispanic patients) had higher surgery rates than Non-Hispanic Whites. Advanced disease and older age predicted non-surgical management. These findings suggest complex interactions between clinical factors and healthcare access that warrant further investigation to optimize treatment selection and address potential inequities in bladder cancer care.

Disitamab vedotin plus PD-1 inhibitors as neoadjuvant therapy for cisplatin-ineligible muscle-invasive bladder cancer: A real-world retrospective study.

691 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) remains the standard for muscle-invasive bladder cancer (MIBC), improving 5-year overall survival by about 8%. However, many patients with renal impairment or poor performance status cannot tolerate cisplatin. Disitamab Vedotin (DV), a HER2-targeted antibody–drug conjugate, has shown encouraging efficacy and safety in metastatic urothelial carcinoma. This study evaluated the efficacy of DV combined with PD-1 inhibitors as NAC in cisplatin-ineligible MIBC. Methods: We retrospectively analyzed 40 patients with pathologically or radiologically confirmed MIBC (T2–4N0–1M0) who were ineligible for cisplatin due to renal dysfunction or chemotherapy intolerance. Treatment regimens included DV (2 mg/kg every 2 weeks) plus pembrolizumab, tislelizumab (200 mg every 3 weeks), or toripalimab (3 mg/kg every 3 weeks). Primary endpoints were pathological complete response (pCR) and clinical complete response (cCR); the secondary endpoint was disease-free survival (DFS). Results: Among 40 enrolled patients (70% male), HER2 IHC was 1+ in 1 case (2.5%), 2+ in 20 (50%), and 3+ in 19 (47.5%). The median number of DV cycles was 5 (range 4–6). After NAC, 27 patients underwent radical cystectomy (RC), and 13 received bladder-preserving therapy. pCR was achieved in 10/27 RC patients (37.0%), and cCR in 10/13 bladder-preserving patients (76.9%), yielding a total CR rate of 50%. The 1-year DFS rate was 95%. Conclusions: DV combined with PD-1 inhibitors as neoadjuvant therapy showed high complete response rates and favorable short-term survival in cisplatin-ineligible MIBC. This regimen may offer an effective and bladder-sparing therapeutic alternative for patients unfit for standard cisplatin-based chemotherapy.

Development of cardiovascular disease risk factors in patients with prostate cancer initiating novel hormonal therapies (NHTs): Real world evidence.

146 Background: Novel hormonal therapies (NHTs), abiraterone acetate, enzalutamide, apalutamide, and darolutamide, target the androgen receptor axis and have become the standard of care for patients with advanced prostate cancer. Although NHTs have a generally tolerable side effect profile, cardiovascular system toxicities are a known and under-researched treatment-related adverse event, with limited real-world data available. Methods: A retrospective cohort study was conducted among patients with advanced prostate cancer, who initiated an NHT between January 2022 and August 2025 at our academic center. The study assessed the incidence of initiating new antihypertensive, lipid-lowering, or antidiabetic medications following NHT initiation. Results: Baseline characteristics are summarized in Table 1. 195 patients were included in this study. 87/195 (44.6%) of patients were on abiraterone acetate, 11/195 (5.6%) on apalutamide, 80/195 (41.0%) on darolutamide, and 17/195 (8.7%) on enzalutamide. Incidence of initiation of a new anti-hypertensive medication after NHT start was 20/87 (30.0%) of patients in the abiraterone acetate group, 2/11 (18.2%) in the apalutamide group, 13/80 (16.3%) in the darolutamide group, and 2/17 (11.8%) in the enzalutamide group. Incidence of initiation of a new lipid-lowering medication after NHT start was 16/87 (18.4%) of patients in the abiraterone acetate group, 2/11 (18.2%) in the apalutamide group, 8/80 (10.0%) in the darolutamide group, and 2/17 (11.8%) in the enzalutamide group. Incidence of initiation of a new diabetes medication after NHT start 19/87 (21.8%) of patients in the abiraterone acetate group, 1/11 (9.1%) in the apalutamide group, 17/80 (21.3%) in the darolutamide group, and 2/17 (11.8%) in the enzalutamide group. Conclusions: Although baseline characteristics of hypertension, hyperlipidemia and diabetes mellitus were roughly comparable the abiraterone acetate and darolutamide groups, patients initiating abiraterone acetate demonstrated higher rates of initiation of antihypertensive and lipid-lowering medications compared to those receiving darolutamide. However, the need for initiation of new diabetes medication was comparable between these two groups. Baseline prevalence of hypertension (HTN), hyperlipidemia (HLD) and diabetes mellitus (DM) per NHT group. HTN HLD DM Abiraterone acetate 54/87 (62.1%) 43/87 (49.4%) 22/87 (25.3%) Apalutamide 7/11 (63.6%) 5/11 (45.5%) 5/11 (45.5%) Darolutamide 46/80 (57.5%) 43/80 (53.8%) 23/80 (28.9%) Enzalutamide 9/17 (52.9%) 11/17 (64.7%) 8/17 (47.1%)

Multifunctional Self‐Assembling Peptide System for Preventing Noise‐Induced Hearing Loss

ABSTRACT Functional self‐assembling peptides prepared by linking short functional peptides to basic self‐assembling peptides via solid‐phase synthesis are often single‐function and insufficient for preventing complex diseases, including noise‐induced hearing loss (NIHL). Herein, a strategy to design multifunctional self‑assembling peptides (NPR36) for preventing NIHL is presented. Compared to the conventional approach of constructing multifunctional self‐assembling peptide systems through co‐assembling distinct functional peptides, this strategy integrates multiple functions into a single self‐assembling peptide by conjugating multifunctional hormone‐derived peptides with extended basic self‐assembling peptides. This monolithic integration eliminates the need to balance concentration ratios and prevents efficacy loss that occurs when the concentration of any component drops below its therapeutic threshold, while also ensuring that each peptide possesses complete multifunctionality, thereby enhancing therapeutic effects. Benefiting from the non‐covalent interactions of the extended assembly motif, NPR36 self‑assembling peptides can form nanofibers and achieve sustained release during disassembly, maintaining an effective concentration at the treatment site. Furthermore, a fiber‐microalgae complex was formed by combining NPR36 with Spirulina platensis. This fiber‐microalgae‐based system synergistically exerted antioxidant and anti‐apoptotic effects, markedly reducing hair cell loss and restoring hearing. Overall, preventive interventions based on multifunctional self‐assembling peptides could overcome the clinical translation challenges in the prevention of inner ear disorders.

High Concentration Antibody Formulations Enabled via Thermostable Ionic Liquids

ABSTRACT Concentrated protein formulations have garnered significant attention in both commercial and research domains due to their relevance in patient‐favored, subcutaneous administration. However, these formulations face challenges such as high viscosity and elevated potential for aggregation, primarily driven by intermolecular electrostatic and hydrophobic protein‐protein interactions (PPIs). Achieving an acceptable injectability profile (<20 cP) often necessitates the incorporation of excipients that mitigate PPIs through shielding effects. Current clinical formulations exhibit a narrow colloidal stability window, largely due to molecular changes under physical and thermal stress, whilst also suffering from suboptimal bioavailability (50%–85%). To address these limitations, we harness the utility of ionic liquids (ILs) that offer tunable charge and amphiphilicity profiles as a means to simplify and stabilize protein formulations. Herein, we synthesized biocompatible choline and organic acid‐based ILs and assessed their viscosity profiles with IgG antibody at both high (90 mg/mL) and ultra‐high (230 mg/mL) concentrations. Functional and structural stability assays conducted over 4 months at room temperature identified promising IL candidates for in vivo studies at both IgG concentrations. Through a multi‐tiered screening strategy, we generated thermally stable, ultra‐high concentration antibody solutions that achieved a five fold improvement in serum absorption of polyclonal IgG compared to their saline solutions.