Browse Articles

Interaction between obesity and vitamin D and testosterone and vitamin D in prostate cancer patients on active surveillance in the PROVENT trial.

401 Background: PROVENT was a multicentre double blind 3x2 placebo controlled phase II trial to evaluate Vitamin D and Aspirin in low risk prostate cancer during active surveillance. This planned translational research, reports results on levels of obesity in the cohort and investigates the interaction of obesity on pre-trial Vitamin D and Testosterone levels. Methods: Details of the trial are published elsewhere (DOI: 10.1002/bco2.169). The trial protocol (https://www.isrctn.com/ISRCTN91422391) was approved by National Research and Ethics Service (REC reference 14/LO/2033). Blood taken before starting treatment was stored in onsite tissue bank (doi.org/10.3390/cancers17010070). Statistics on median weight and Vitamin D levels and testosterone and vitamin D levels have been studied by Wilcoxon Sum Rank test and Chi-squared test. Results: 104 patients were recruited in 10 months. 52% (54/104) were overweight (BMI 25-29.9) and 22% (23/104) obese (BMI=>30). The median weight was 83.6 kilos. Those with a weight lower than the median had >35 nanomol/L Vitamin D in 75% (38/48) while those with a weight => median had =< 35 nanomol/L Vitamin D in 41.2% (21/51, X 2 3.86, p< 0.05). Study of Vitamin D and Testosterone interaction showed a non-significant trend for more patients with Testosterone <12 nmol/L in those with <50ng/ml vitamin D (12/17=41.4%) than those with ≥50 ng/ml (15/31=31.6% X 2 =pNS). Conclusions: Though the data presented did not produce strong statistically significant findings, in both Vitamin D and obesity and Vitamin D and testosterone studies the % difference was equal to the % difference in meta-analyses reporting statistical significance for 100 times larger patient numbers. Given that overweight and obesity predictors poor outcome and Chandler, D. et al 2020 demonstration that Vitamin D supplements did not reduce incidence of cancer in overweight and obese subjects, further studies of vitamin D and the new obesity drugs GLP-1RA in prostate cancer are justified.

Global cancer statistics for children: Two decades of change and projections to 2050

Abstract Reliable, contemporary estimates of the global childhood cancer burden remain scarce, particularly in the post‐coronavirus disease 2019 (COVID‐19) era. By using data from the Global Burden of Disease 2021 and Global Cancer Observatory 2022 projects, the authors evaluated the childhood cancer burden at global, regional, and national levels, characterizing temporal and projected trends, and analyzed the data according to disparities by geography and socioeconomic development. From 2000 to 2021, the age‐standardized incidence rate (ASIR) and the age‐standardized mortality rate (ASMR) of childhood cancer declined overall (average annual percent change, −0.88 and −2.13, respectively), especially during the COVID‐19 pandemic. During this period, the disparities in childhood cancer burden were mainly concentrated in countries/territories with a lower Sociodemographic Index. In 2022, an estimated 202,164 new cases and 77,182 deaths from childhood cancer occurred worldwide (ASIR and ASMR, 10.3 and 3.9 per 100,000 children, respectively). Countries/territories with higher a Human Development Index (HDI) had a higher incidence (ASIR, 8.0 [low HDI] vs. 15.3 [very high HDI] per 100,000), whereas those with a lower HDI had higher mortality (ASMR, 4.4 [low HDI] vs. 2.8 [very high HDI] per 100,000). Analyses indicated that, by 2050, there will be 204,925 projected new cases and 78,210 deaths globally, with increases only in low HDI countries/territories, exacerbating existing health inequities. Childhood cancer remains a global health challenge, with notable geographic and socioeconomic disparities. These data serve as the impetus for governments and policymakers to prioritize resources and equitable access to interventions, particularly in regions with lower levels of development, while addressing health care vulnerabilities exposed by global crises like the COVID‐19 pandemic.

Turning Sunlight and Seawater Into Energy: Photocatalytic Hydrogen Peroxide as a Green Fuel Carrier

ABSTRACT Hydrogen peroxide (H 2 O 2 ) is an emerging green energy carrier and a versatile oxidant. Its production, however, remains heavily reliant on the energy‐ and waste‐intensive anthraquinone process. In contrary, photocatalysis provides a sustainable pathway for the preparation of H 2 O 2 by utilizing oxygen (O 2 ) and water (H 2 O) as feedstocks. In this aspect, since seawater is the most abundant water resource on the earth, utilization of seawater for the generation of H 2 O 2 will have great potential in this field. However, the complex composition and high salt content of seawater pose significant challenges to the photocatalytic process, such as catalyst deactivation and interference with the reaction pathway. In this review article, we have summarized recent advances in the photocatalytic synthesis of H 2 O 2 directly from seawater. We have initially introduced the basic principle of photocatalytic reaction and the interaction between the components in seawater and the photocatalyst. Then, according to the different types of photocatalysts, we have discussed the research progress, their advantages, and limitations in the synthesis of H 2 O 2 . Finally, we have provided the current technological bottlenecks and foreseen future research directions. In summary, this review article will provide a comprehensive understanding of the generation of H 2 O 2 directly from seawater.

Meissner Effect and Nonreciprocal Charge Transport in Non‐Topological 1T‐CrTe ₂ /FeTe Heterostructures

ABSTRACT Interface‐induced superconductivity has recently been achieved by stacking a magnetic topological insulator layer on an antiferromagnetic FeTe layer. However, the mechanism driving this emergent superconductivity remains unclear. Here, we employ molecular beam epitaxy to grow a 1T‐CrTe 2 layer, a 2D ferromagnet with a Curie temperature up to room temperature, on a FeTe layer. These 1T‐CrTe 2 /FeTe heterostructures show superconductivity with a critical temperature of ∼12 K. Through magnetic force microscopy measurements, we observe the Meissner effect on the surface of the 1T‐CrTe 2 layer. Our electrical transport measurements reveal that the 1T‐CrTe 2 /FeTe heterostructures exhibit nonreciprocal charge transport behavior, characterized by a large magneto‐chiral anisotropy coefficient. The enhanced nonreciprocal charge transport in 1T‐CrTe 2 /FeTe heterostructures provides a promising platform for exploring the magnetically controllable superconducting diode effect.

Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study.

LBA417 Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti–PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were ≥18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti–PD-(L)1 therapy or ≤6 mo of last dose of adjuvant anti–PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9–39.8) at IA1, and 29.0 mo (19.3–49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0–44.3+) with bel + lenva vs 12.3 mo (1.8+–35.9+) with cabo at IA2. Grade ≥3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti–PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2α inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231 . IA1 IA2 Bel + Lenva, N = 371 Cabo, N = 376 Bel + Lenva, N = 371 Cabo, N = 376 Median PFS (95% CI), mo 14.6 (11.1–16.6) 10.6 (9.2–11.1) 14.8 (11.2–16.6) 10.7 (9.2–11.1) HR (95% CI) 0.74 (0.61–0.89) 0.70 (0.59–0.84) P value (1-sided) .00095* .00007* Median OS (95% CI), mo NR (26.5–NR) 27.4 (23.6–31.4) 34.9 (27.5–NR) 27.6 (24.0–31.4) HR (95% CI) 0.90 (0.70–1.15) 0.85 (0.68–1.05) P value (1-sided) .19322 .06075 ORR, % (95% CI) 52.6 (47.3–57.7) 39.6 (34.6–44.8) 52.6 (47.3–57.7) 40.2 (35.2–45.3) P value (1-sided) .0002* NA NA, not applicable. *Denotes statistical significance.

Synergistic efficacy of gedatolisib and darolutamide in prostate cancer to overcome resistance to androgen-targeted therapy.

383 Background: The PI3K/AKT/mTOR (PAM) pathway is frequently dysregulated in prostate cancer (PC), often in association with the loss of PTEN. Since PAM pathway activation is a key adaptive resistance mechanism to androgen-targeted therapy, concomitant inhibition of both the PAM pathway and the androgen receptor (AR) pathway is a promising treatment strategy for castration resistant PC (CRPC). However, many current inhibitors that only target single PAM pathway components have limited effectiveness because other components of the pathway can circumvent their activity. Our prior research showed that gedatolisib, a multi-target PAM inhibitor that targets all Class I PI3K isoforms and mTORC1/2, exerts greater growth inhibitory effects than single-target inhibitors in PC cell lines, irrespective of their PTEN or AR status. In the present study, we tested gedatolisib in combination with darolutamide in PC cell models. Methods: The cellular and molecular effects of the gedatolisib/darolutamide combination were tested in both PTEN-positive and PTEN-deficient PC cell lines. AR-positive PC lines adapted to long-term darolutamide treatment were also developed to model progression after AR-targeted therapy. To assess the effects of gedatolisib, darolutamide, or their combination, multiple assays were employed, including GR metrics analysis, flow cytometry analysis of PAM pathway activity, cell cycle and death, analysis of glucose and lipid metabolism, and qPCR analysis of AR, AR-target genes, and E2F-target genes. Results: The combination of gedatolisib and darolutamide demonstrated stronger anti-proliferative and cytotoxic effects across most AR-positive PC cell lines compared to either drug alone, regardless of the cells’ PTEN status. Mechanistically, the drug combination blocked cell cycle progression and DNA proliferation in association with decreased E2F-target gene transcription, induced apoptosis, and reduced glucose and lipid metabolism. Importantly, the combination was effective in cell lines adapted to darolutamide, suggesting a potential benefit for prostate tumors that have progressed following androgen-targeted therapies. Conclusions: The combination of gedatolisib and darolutamide shows a combinatorial benefit in multiple AR-positive PC cell models, regardless of PTEN status or sensitivity to AR inhibitors. These results provide a strong mechanistic rationale for clinical studies evaluating gedatolisib in combination with AR inhibitors in CRPC.

Association of ctDNA status with upstaging, pathologic outcomes, and genomic alterations in high-risk NMIBC.

831 Background: The role of circulating tumor DNA (ctDNA) in non–muscle-invasive bladder cancer (NMIBC) remains incompletely defined. In high-risk and Bacillus Calmette–Guérin (BCG)–exposed disease, ctDNA detection and genomic profiling may provide insight into disease biology and guide management. We evaluated ctDNA positivity rates and their association with genomic alterations, clinical upstaging, and pathologic outcomes in patients with high-risk NMIBC. Methods: We retrospectively reviewed 44 patients with histologically confirmed high-risk NMIBC (per AUA criteria) treated at a single institution between 2022-2025. Among BCG-exposed patients, BCG status was categorized as unresponsive per FDA definitions. ctDNA testing was performed using a personalized, tumor-informed assay (Signatera, Natera) at baseline and every 3 months; positivity was defined as detection of ≥2 tumor-specific variants. Comprehensive genomic profiling (CGP) with the Altera assay (Natera) was incorporated when available. Clinical upstaging was defined as progression to ≥cT2 or cN+ disease, and pathologic outcomes after radical cystectomy were evaluated by final stage and nodal status. Results: A total of 44 patients with HR-NMIBC were included (median age 69 years, IQR 59–75); 85% were male and 70% had pure urothelial carcinoma. Median follow-up was 8.2 months (IQR 4.7–11.7). BCG-naïve and BCG-exposed cohorts comprised 55% and 45% of patients, respectively, with 65% of the latter classified as BCG-unresponsive. At presentation, 93% had T1, 5% Tis, and 2% Ta disease; concomitant CIS was observed in 19%. ctDNA positivity was detected in 30% (6/24) of BCG-naïve and 40% (8/20) of BCG-exposed patients. Following clinical and radiologic assessment, upstaging occurred in 36% (5/14) of ctDNA-positive versus 10% (3/30) of ctDNA-negative patients. Overall, 36% (16/44) underwent radical cystectomy; 44% (7/16) were ctDNA-positive, of whom 86% (6/7) had muscle-invasive or locally advanced disease (≥pT2b or pN+), while one had pT1pN0. In contrast, all ctDNA-negative patients (9/9) had negative nodal status (4 pT0N0, 4 < pT1N0, and 1 pT2aN0). Among the 23 patients with available CGP, 8 were concurrently ctDNA-positive. TP53 mutations were more common in ctDNA-positive versus ctDNA-negative patients (88% vs 33%), whereas FGFR3 alterations were less frequent (0% vs 40%). Conclusions: ctDNA positivity in HR-NMIBC correlated with higher rates of clinical upstaging and adverse pathologic findings, including muscle-invasive and nodal disease at cystectomy, whereas ctDNA negativity was largely confined to non-invasive pathology. TP53 enrichment among ctDNA-positive patients suggests a biologically distinct and potentially more aggressive subset. These findings support the potential role of ctDNA as a biomarker for disease biology and risk stratification in HR-NMIBC.

Improved survival, disparate outcomes contemporaneously define the modern worldwide burden of childhood cancers

Scalable Solar Evaporator Based on Bandgap Engineered CuMnCrO ₄ Spinel Oxide with Salt‐Resistant Property for Contaminated Seawater (Adv. Mater. 17/2026)

A Recyclable Polythioester With <i>α</i> ‐Gem‐Dimethyl Substitution: Instantaneous Crystallization Triggered by Large and Rapid Stretching

ABSTRACT Designing and fabricating recyclable polymers combining closed‐loop depolymerizability with high mechanical performance remains a major challenge in sustainable materials. To reach both high recyclability without compromising the mechanical properties, precise controlling of the crystallization behaviors emerges as a crucial strategy. Here, we demonstrate unexpected crystallization behavior in a depolymerizable polythioester (PTE), PaGMTE, and report the first crystal structure of this kind. Derived from organocatalytic ring‐opening polymerization of α ‐gem‐dimethyl‐ β ‐thiolactone, PaGMTE exhibits exceptionally slow quiescent crystallization, which stands in sharp contrast to its polyester analog polypivalolactone that crystallizes rapidly. However, large‐amplitude rapid stretching (strain ~600%, strain rate ≥ 10 s −1 ), where the Deborah number based on the Rouse time of entanglement strand exceeds 1, triggers its crystallization, accelerating the crystallization rate by &gt; 200,000 fold and achieving ~40% crystallinity within 1 s. This approach yields highly oriented fibers with outstanding mechanical properties (Young's modulus of 0.80 GPa, tensile strength of 120 MPa, breaking strain of 70%), high transparency, and the potential as a waveguide. We unveil PaGMTE's orthorhombic crystal structure (space group P 2 1 2 1 2 1 , a = 1.075 nm, b = 0.622 nm, c = 3.618 nm) with antiparallel‐packed homochiral 8 3 helices. The slow quiescent crystallization shall arise from entropic barriers associated with conformational adjustments toward the helix. Our findings highlight sulfur substitution's profound impact on polymer properties and prove that significantly enhancing the crystallization process holds promise for making PTE a high‐value‐added recyclable material.

EV-PRIME: Phase Ib/II study of enfortumab vedotin and pembrolizumab combined with radiotherapy as a bladder-sparing trimodality therapy in muscle invasive bladder cancer.

TPS885 Background: Enfortumab vedotin and pembrolizumab (EVP) combination is highly effective for patients with metastatic urothelial cancer, with a response rate of 68% that includes many durable responses. This combination has also demonstrated activity in the perioperative setting for patients with muscle-invasive bladder cancer (MIBC), based on results of the KEYNOTE-905/EV-303 trial. Current standard of care treatment for patients with MIBC remains systemic therapy followed by radical cystectomy (RC). However, for selected patients who are either not RC candidates or prefer a bladder-sparing approach, trimodality therapy (TMT) with trans-urethral resection of bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy (RT) constitutes an alternative treatment option. The efficacy and durable responses observed with EV/P support the rationale of combining this regimen with RT for patients with MIBC, allowing patients to potentially forego extensive surgery. Methods: This is a phase Ib/II, multi-center, investigator initiated trial of bladder sparing tri-modality therapy in MIBC, utilizing EVP in combination with standard fractionation bladder RT following TURBT (within 8 weeks of treatment start). Eligible patients have biopsy-confirmed MIBC (cT2-T4a) with component of urothelial histology, but no evidence of metastatic disease on imaging (M0) and have ECOG PS ≤1. Patients will be either ineligible for RC or declining surgery and will not have contraindications to receiving either EV or P. Enrolled patients will receive 2 cycles (6 weeks) of treatment with combination of EVP and concurrent conventionally fractionated RT (64Gy/32Fx), followed by adjuvant EV for 3 cycles (5 total cycles maximum) and pembrolizumab for 15 cycles (17 total cycles maximum). The trial will start with a phase Ib 3+3 dose escalation of EV at three dose levels (0.75 mg/kg, 1.00 mg/kg, 1.25 mg/kg) given on Days 1,8 of a 21-day cycle, in combination with standard dose of pembrolizumab 200 mg IV (Day 1 of 21-day cycle) and RT, to define the safety of this combination and determine the recommended phase II dose (RP2D) of EV as part of this regimen. In the phase II portion of the study, patients will be treated at the RP2D of EV in combination with standard dose of pembrolizumab and RT, to assess the efficacy of this combination. Primary efficacy endpoint is the 6-month clinical complete response (cCR) in the phase II portion of the study; important secondary endpoints include median recurrence-free survival, median cystectomy-free survival and median overall survival. The study is open and currently actively accruing patients in phase Ib dose escalation at UCSF. This trial will aim to enroll 35 patients at the RP2D, and up to 47 patients total at 3 high-volume centers. Clinical trial information: NCT06470282 .

Quality of life assessment during prostate cancer radionuclide therapy: Updated FACT-RNT psychometric evaluation.

141 Background: The Functional Assessment of Cancer Therapy–Radionuclide Therapy (FACT-RNT) is a 15-item patient-reported outcome (PRO) measure used to monitor RNT-related symptoms, toxicities, and quality-of-life impacts in patients with metastatic castrate-resistant prostate cancer (mCRPC). This study re-examined the validity and reliability of the FACT-RNT using repeated assessments in an expanded, multi-institutional cohort of patients receiving RNT. Methods: Patients starting 177 Lu-PSMA-617 for mCRPC at UCLA from December 2022 to August 2023 and at Moffitt Cancer Center from October 2023 to October 2025 completed the FACT-RNT before each cycle. Patients at Moffitt also completed previously validated measures of prostate cancer disease- and treatment-related symptoms (NFPSI-17) and physical function (PG-SGA). Reliability was assessed through tests of internal consistency, split-half reliability, inter-item correlations, and test-retest reliability across RNT cycles 1-4. Correlations between the FACT-RNT and both the NFPSI-17 and PG-SGA at cycle 2 were calculated to assess convergent validity. Results: Patients (N=81) were predominantly non-Hispanic (80%) and White (69%), and were, on average, 70 years old (SD=9, range=43-91) at RNT cycle 1. Fifty-nine (73%) completed the FACT-RNT for ≥2 cycles, and 33 (41%) completed the FACT-RNT for ≥4 cycles. Internal consistency reliability across cycles was good-to-excellent (α=0.83-0.90), average split-half reliabilities were excellent (α=0.82-0.86), and average inter-item correlations were acceptable ( r =0.24-0.30). Test-retest reliability was moderate-to-good for individual cycle scores (ICC3,1=0.68, CI=0.53-0.81, p&lt;0.001) and excellent when averaging across cycles 1-4 (ICC3,4=0.89, CI=0.82-0.94, p&lt;0.001). FACT-RNT total score correlations between consecutive cycles were also strong (cycles 2-3, r =0.72; cycles 3-4, r =0.91). For patients completing other PROs at cycle 2 (n=23), the FACT-RNT was positively associated with symptoms as assessed by NFPSI-17 ( r =0.89, p &lt;0.001) and negatively associated with physical functioning assessed by PG-SGA ( r =-0.61, p &lt;0.002), suggesting strong convergent validity. Conclusions: Results from updated analyses suggest that the FACT-RNT has good-to-excellent internal consistency and split-half reliability, acceptable inter-item correlations, and moderate-to-excellent stability across administrations. As between-cycle variability in treatment-related symptoms is expected, these findings may reflect both true change in treatment-related symptoms and quality of life, and measurement reliability. The FACT-RNT also correlated as expected with related PRO measures, supporting preliminary convergent validity. Overall, this evidence supports the validity and reliability of the FACT-RNT and its use in future research and clinical practice.

Prostate cancer in patients with HIV: A multisite retrospective cohort study.

326 Background: Advances in highly active antiretroviral therapy (HAART) have markedly improved the life expectancy of people living with HIV (PLWH). As this population ages, prostate cancer (PCa) is expected to become one of the most common malignancies. Although studies show a lower incidence of PCa in PLWH, early evidence suggests more advanced disease at presentation and higher mortality. This study characterizes the demographics and survival outcomes of PLWH diagnosed with PCa. Methods: A retrospective cohort study using the TriNetX US Collaborative Network, comprising de-identified EHR data from over 131 million patients. Men aged 18 to 90 with PCa were stratified by HIV status. Those with another malignancy within one year, excluding non-melanoma skin cancer, were excluded. Demographics, treatments, and outcomes were analyzed using 1:1 propensity score matching, Chi-square tests, Kaplan-Meier survival, and Cox proportional hazards models. Results: Among 625,752 patients included in the study, 1,645 were PLWH. Compared with the cohort without HIV, PLWH diagnosed with PCa were younger at diagnosis (mean age 62 vs. 67 years), more likely to be Black or Hispanic, and more often received care at hospitals in the Southern United States ( p &lt; 0.001). PLWH with PCa also exhibited higher rates of comorbid conditions, including diabetes, hypertension, and obesity ( p &lt; 0.001). After propensity score matching, 3-year survival was significantly lower among PLWH ( p &lt; 0.05), with a mean follow-up of approximately 4 years in both groups (Table 1). Incomplete pathologic reporting (i.e. &lt;10% in each cohort) limited further characterization of the clinical stage and Gleason grade group. Conclusions: PLWH who develop PCa represent a distinct clinical population characterized by younger age at diagnosis, greater comorbidity burden, and lower post-diagnosis survival compared to patients without HIV. These findings highlight the need for tailored PCa screening, management, and survivorship strategies for PLWH to address disparities in outcomes. Future directions will focus on outcomes after specific treatments such as surgery and radiation in PLWH. Kaplan-Meier survival of patients with prostate cancer (PCa) by HIV status. 1 year 2 years 3 years 4 years PCa + HIV 96.3% 93.3% 91.4%* 89.8%* PCa (- HIV) 96.3% 95.1% 93.9%* 92.2%* Kaplan-Meier estimates of overall survival at 1, 2, 3, and 4 years following diagnosis of PCa, after 1:1 propensity score matching. * p &lt; 0.05

Light‐Driven Reconfigurable Logic in a Monolithic Perovskite Device via Nonlinear Photoresponse Switching (Adv. Mater. 14/2026)

Genomic and clinical correlates of belzutifan treatment in renal cell carcinoma (RCC): A retrospective analysis of 240 RCC patients.

528 Background: Belzutifan is a HIF-2α inhibitor approved for the treatment of advanced RCC, targeting the hypoxia signaling pathway central to tumor progression. While initial clinical trials demonstrated efficacy, predictive biomarkers remain undefined. Methods: Comprehensive DNA (592-gene panel or whole exome) and RNA (whole transcriptome) sequencing were performed on RCC samples via Caris Life Sciences. Patient samples with clear cell histology or VHL mutation in non-clear cell histology were considered for the study. Time-on-treatment (TOT) data for Belzutifan were extracted from insurance claims, and patients were stratified as responders or non-responders based on the median TOT. Results: In a cohort of 2,538 RCC patients, 240 patient samples were identified to have received Belzutifan (majority treated after biopsy) and were stratified into responders (n = 109) and non-responders (n = 131) based on median TOT (77 days; 95% CI: 62–84 days). No statistically significant differences were observed between the two groups across a range of clinical and demographic variables. Median age was 60 years in responders and 62 in non-responders. The proportion of metastatic biopsies was 61.1% in non-responders vs 58.7% in responders. Genomic profiling revealed high prevalence of VHL mutations in both groups (94.4% in responders vs. 92.8% in non-responders). Responders exhibited enrichment for alterations in the PI3K/AKT/mTOR pathway, including PIK3CA (12.4% vs. 3.3%), PIK3CB (6.7% vs. 1.9%), PIK3R1 (4.8% vs. 0.8%), and PTEN (13.2% vs. 9.8%). Mutations in DNA damage response genes were also more common in responders, particularly STAG2 (6.7% vs. 0%) and ATM (4.8% vs. 0.8%). In contrast, non-responders showed higher frequencies of BAP1 (17.7% vs. 12.2%), ARID1A (8.3% vs. 2.9%), NF2 (4.0% vs. 1.9%), and KDM5C (14.6% vs. 11.8%). None of these differences were statistically significant, and no single mutation was unique to either group, suggesting response may depend on combined or pathway-level alterations rather than individual genes. Transcriptomic analysis of HIF pathway genes revealed subtle numerical differences: slightly higher EPAS1 expression in responders (median: 7.73 vs. 7.54) and CA9 (4.82 vs. 4.46). Expression of other genes such as HIF1A, ARNT, ARNT2, and HIF3A showed minor variation between groups, with HIF1A and HIF3A slightly numerically higher in non-responders. Conclusions: Belzutifan response in RCC may relate to PI3K/AKT/mTOR and DNA damage response alterations, whereas resistance may involve chromatin remodeling mutations. Minimal clinical or demographic differences support broad trial inclusion, though subtle HIF-pathway and mutational patterns suggest molecular markers warranting prospective validation.

RNDO-564-001: A first-in-human, phase 1/1b study of RNDO-564, a bispecific antibody for the treatment of advanced bladder cancer and other tumors associated with Nectin-4 expression.

TPS903 Background: RNDO-564 is a novel CD28 x Nectin-4 bispecific antibody (bsAb) with a high affinity Nectin-4 binding arm and a potency-optimized CD28 arm designed for maximum therapeutic window. RNDO-564-001 (NCT07218003) is an ongoing, open label, multicenter, dose escalation and dose optimization study of RNDO-564 as monotherapy, and in combination with pembrolizumab (anti-programmed death [PD]-1 monoclonal antibody), in adults with relapsed/refractory (R/R), locally advanced or metastatic urothelial cancer (la/mUC) and other solid tumors associated with Nectin-4 expression. Methods: The objectives of the study are to assess the safety, tolerability, and to determine the recommended phase 2 dose (RP2D) of intravenous RNDO-564 monotherapy given on Days 1, 8, and 15 of a 21-day cycle. Monotherapy dose escalation will include an accelerated titration component using four single participant (pt) cohorts, followed by more gradual dose increments tested using a Bayesian Optimal Interval (BOIN) with backfill design. To determine the RP2D of single agent RNDO-564 in R/R la/mUC, up to two 20 pt dose optimization cohorts at two different dose levels and/or dosing schedules, will be enrolled. Pts with R/R la/mUC, cervical, head and neck, esophageal, gastric, gastroesophageal (GEJ), non-small cell lung, or triple negative breast cancer, who have exhausted, are ineligible for, or declined available standard treatment options, are eligible for the dose escalation phase of the study. Pts must have an ECOG performance status of 0-1. Pts with prior Nectin-4 directed therapies and MMAE exposure and those with ongoing Grade ≤ 2 peripheral neuropathy are eligible. Pts with a history of, or with active, inflammatory skin conditions are ineligible. Safety endpoints include incidence of adverse events per CTCAE v5.0. Secondary endpoints include clinical activity, pharmacokinetics, and incidence of anti-drug antibody development. Retrospective assessment of Nectin-4 expression on tumor tissue by IHC, and measurement of CD28 receptor occupancy, T cell activation, soluble Nectin-4, and serum cytokines in peripheral blood will be performed as exploratory endpoints. Separate dose escalation and optimization stages in combination with pembrolizumab will be conducted to assess the safety, preliminary clinical activity, and recommended doses for further development of the combination treatment. Additional monotherapy and/or combination therapy expansion cohorts may be opened for participants with non-UC tumors, based on emerging clinical data. Conclusions: RNDO-564-001 is an ongoing phase 1/1b study to determine the safety, tolerability, clinical activity, and RP2D of a novel CD28 x Nectin-4 bsAb that has been optimized for safety and efficacy in R/R la/mUC and other solid tumors associated with Nectin-4 expression. Clinical trial information: NCT07218003 .

Cystectomy-free survival following cretostimogene grenadenorepvec in high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ: Results from the phase 3 BOND-003 trial (Cohort C).

741 Background: A significant treatment gap exists for efficacious, well-tolerated bladder-sparing options for patients with HR BCG-UR NMIBC with CIS. Cretostimogene is an oncolytic immunotherapy with dual mechanisms of action. It replicates in and lyses cancer cells with Rb-E2F pathway alterations, while simultaneously amplifying an anti-tumor immune response, further mediated by the GM-CSF transgene. BOND-003 (NCT04452591) is a phase-3 study evaluating the efficacy and safety of cretostimogene in patients with HR BCG-UR NMIBC with CIS +/- HG Ta/T1 (Cohort C) and HG Ta/T1 only (Cohort P). We report data on radical cystectomy performed post-recurrence or progression on Cohort C. Methods: 112 patients were enrolled. Participants had previously received adequate BCG and were considered BCG-UR by the FDA definition. Cretostimogene treatment consisted of a 6 weekly induction course, followed by 3 weekly maintenance cycles every 3 months at year one and every 6 months during years 2-3. Repeat induction was permitted at Month 3, if persistent HG Ta or CIS. Response assessments included serial cystoscopy, urine cytology, and mandatory mapping biopsy at 12 mo, with centralized review of all pathology. The primary endpoint was Complete Response (CR) at any time. Cystectomy-Free Survival (CFS) and Progression-Free Survival (PFS) were key secondary endpoints. Results: As of the June 23, 2025 data cutoff (median follow-up of 25.8 months), the CR rate at any time is 75.5% (83/110) (95% CI 66.3-83.2%). Kaplan-Meier estimates of 12- and 24-month DoR are 64.2% (95% CI 52.5-73.8%) and 60.1% (95% CI 48.2-70.0%), respectively, with a median DoR of 27.9 months (95% CI 14.3-NE%) and ongoing. The 12- and 24- month CR rate is 46.4% (51/110) (95% CI 36.8-56.1%) and 41.8% (46/110) (95% CI 32.5-51.6%), respectively. The 12- and 24-month CFS rates are 89.2 (95% CI 81.3-93.9) and 81.3% (71.8-87.8), respectively, with median CFS not reached. Among 18 patients who underwent radical cystectomy post-disease recurrence or progression; 15 (83.3%) had NMIBC or pT0 on final pathology. At 12- and 24- months, 96.6% are free from ≥T2 progression. Cretostimogene has a well-tolerated safety profile, with no grade ≥3 treatment-related adverse events. Conclusions: Cretostimogene offers distinct advantages with its mechanism of action, efficacy, durability and safety profile for the treatment of HR BCG-UR NMIBC. Furthermore, a significant proportion of patients receiving cretostimogene remained progression-free and avoided radical cystectomy. Most patients who underwent radical cystectomy had NMIBC or pT0 on final pathology maintaining a window of opportunity. Ongoing and future investigations of cretostimogene, as monotherapy and in rational combinations, may address the considerable unmet need for patients with bladder cancer. Clinical trial information: NCT04452591 .

PIP4K2C: an emerging fulcrum for multiple diseases

Rational Design of 3D Morphable Color‐shifting Mesosurfaces Using Bioinspired Janus Micro‐ and Nanolattices (Adv. Mater. 13/2026)

Bond‐Mode Engineering in Copper(I) Halides: From Excitation‐Dependent Luminescence to High‐Resolution X‐Ray Imaging Screens

ABSTRACT Copper(I)‐based halides are promising for X‐ray detection due to their excellent scintillation efficiency and solution processability. However, the structure–property relationship remains elusive, and their practical viability for X‐ray imaging is largely unverified. In this work, we employ a bond‑mode control strategy to synthesize two compounds from the same amine precursor: ionic (4‑ATHP) 2 CuI 3 and coordinative (4‑ATHP) 4 Cu 4 I 4 (4‐ATHP = 4‐Aminotetrahydropyran), providing a model system to study their photophysics and underlying mechanism. (4‑ATHP) 2 CuI 3 adopts a unique 1D crystal structure with alternating arrangement of Cu 2 I 6 dimers, which shows excitation‑dependent dual emissions. Experimental and calculation results indicate that the dual emissions originate from the Cu 2 I 6 dimer with a different Cu─Cu bond length. In contrast, the (4‑ATHP) 4 Cu 4 I 4 shows single emission centered at 635 nm, in which the organic component contributes to the excited state. The ionic (4‑ATHP) 2 CuI 3 achieves a much higher light yield (55 923 photons/MeV) than that of the coordinative counterpart (31 866 photons/MeV). Furthermore, a large‑area flexible film (15 × 20 cm 2 ) based on (4‑ATHP) 2 CuI 3 delivers a spatial resolution of 20 lp/mm. Critically, integrating this film into a CMOS imager demonstrates superior dynamic imaging without afterglow, outperforming the commercialized CsI: Tl screen. This study not only deciphers the bond‑mode‑dependent photophysics but also validates a commercial‑grade scintillator, paving the way for high‑performance X‑ray imaging materials.