Excessive lighting is integral to dentists’ daily routines but can impair their vision, affecting personal and professional performance. Most studies focus on acute photodamage, neglecting chronic photo-injury from dental lighting and its impact on the blood-retinal barrier homeostasis. An epidemiological survey involving 14,523 individuals showed dentists had 3.6 times higher odds of vision-related issues compared to other occupations (OR = 3.639, 95% CI: 3.064–4.323). Subsequently, chronic photodamage models in rats were created to accurately simulate dental working conditions. Using systematic imaging and gene analysis, including OCT, tissue clearing technology and RNA-sequencing, dental lighting was found to disrupted both inner and outer blood-retinal barriers, reduced retinal blood vessels, and promoted perivascular macrophage recruitment. Among them, the number of capillary branches decreased sharply. Moreover, the activation of inflammatory-related pathways such as NF-κB signaling resulted in the damage of vision-related functional structures in the retina. Notably, among three dental light sources, low-intensity halogen caused minimal retinal damage, whereas blue and white LEDs significantly disrupted blood-retinal barrier homeostasis. This study explored the potential mechanism of dental lighting environment inducing the disruption of blood-retinal barrier homeostasis, and provided essential guidance for dental professionals in selecting light sources, which is conducive to reducing the risk of occupational ocular diseases among dentists.

e20500 Background: T-DXd (5.4 mg/kg) is approved in multiple countries for pretreated unresectable/metastatic HER2m NSCLC; conditional approval in China was supported by DESTINY-Lung02 (DL-02) and DL-05 results. In DL-02, T-DXd showed encouraging CNS activity in this population. Here, we report a post-hoc analysis of DL-05 assessing T-DXd in pts from China with HER2m NSCLC with/without baseline (BL) CNS mets. Methods: DL-05 (NCT05246514), an open-label, single-arm, Phase 2 study, evaluated T-DXd (5.4 mg/kg Q3W IV) in pts from China with metastatic HER2m NSCLC with disease progression on/after ≥1 prior anticancer therapy. Pts with pretreated asymptomatic / neurologically stable CNS mets were eligible. Brain CT or MRI scans were performed in all pts at BL and study end. Pts with CNS mets had brain scans every 6 weeks from enrollment date to 48 weeks, then every 9 weeks until RECIST 1.1-defined progressive disease. Additional brain scans were carried out as clinically indicated. In pts with/without BL CNS mets, systemic efficacy (confirmed objective response rate [cORR], disease control rate [DCR], duration of response [DOR], and progression-free survival [PFS] by independent central review [ICR] per RECIST 1.1; and overall survival [OS]), CNS-PFS by ICR per CNS-modified RECIST 1.1, and safety were assessed. CNS-cORR, CNS-DCR, and CNS-DOR were evaluated in pts with measurable BL CNS mets. Results: At data cutoff (November 4, 2024), 72 pts had received T-DXd; 30 pts had BL CNS mets, including 10 with CNS-measurable disease. Median (range) duration of follow up for all pts was 20.2 (2–27) months. In pts with and without CNS mets, median (range) treatment duration was 7.6 (0.7–26.9) months and 10.5 (0.7–26.6) months, respectively. Systemic efficacy data and CNS-PFS are in the Table. In pts with measurable CNS mets (n=10), CNS-cORR was 40.0% (95% CI 12.2, 73.8; n=4, one complete response was reported), CNS-DCR was 100% (95% CI 69.2, 100), and median CNS-DOR was not evaluable (NE). Drug-related Grade ≥3 adverse events were reported in 60.0% (n=18) and 52.4% (n=22) of pts with and without CNS mets, respectively. Conclusions: T-DXd showed antitumor activity in pts from China with metastatic HER2m NSCLC with and without BL CNS mets; consistent with previous analyses, promising CNS activity was observed. No new safety signals were reported. Results support T-DXd use in pretreated pts with HER2m NSCLC, including those with CNS mets. Clinical trial information: NCT05246514 . BL CNS mets(n=30) No BL CNS mets(n=42) cORR, % (n)*95% CI 46.7 (14)28.3, 65.7 64.3 (27)48.0, 78.4 DCR, % (n)*95% CI 90.0 (27)73.5, 97.9 92.9 (39)80.5, 98.5 Median DOR, months (95% CI)* 7.1 (5.3, 15.3) 14.0 (5.8, NE) Median PFS, months (95% CI)* 8.0 (5.8, 16.5) 13.0 (7.2, NE) Median CNS-PFS, months (95% CI) 7.8 (5.6, 9.9) NE (NE, NE) Median OS, months (95% CI)* 16.6 (13.3, 21.7) 24.0 (19.9, NE) *Systemic assessment.

BACKGROUND:Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related deaths. Immune checkpoint inhibitors (ICIs) of programmed death-1 (PD-1)/programmed death ligand-1 signaling induce tumor regression in some patients with NSCLC, but most patients with NSCLC exhibit resistance to ICIs therapy. NSCLC shapes the potent tumor immunosuppressive microenvironment (TIME) that underlies tumor immune tolerance and acquired resistance. Therefore, elucidating the cellular and molecular mechanisms by which NSCLC establishes and sustains the TIME is essential for developing novel strategies to overcome immune resistance and enhance the clinical benefit of ICIs. METHODS:The correlation between sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (SAMHD1) expression and ICIs was analyzed via immunohistochemistry. Cell migration assay was performed to assess the effect of SAMHD1 on macrophage recruitment. Multicolor flow cytometry was performed to analyze the effect of SAMHD1 knockdown on the tumor microenvironment. SAMHD1 regulation of the dual specificity phosphatase 6-extracellular regulated protein kinases 1/2 (DUSP6-ERK1/2) pathway was verified by RNA sequencing and western blotting. RESULTS:Here, we identify the SAMHD1 as a potential therapeutic target and a major determinant of poor response to ICIs in patients with NSCLC. Tumors with high SAMHD1 expression show resistance to anti-PD-1 antibody (αPD-1) treatment, whereas tumors with low SAMHD1 expression are highly sensitive. SAMHD1-dependent resistance to αPD-1 is characterized by increased tumor-associated macrophages (TAMs) infiltration and reduced CD8+T cell numbers. Mechanistically, SAMHD1 regulates the expression of macrophage-associated chemokines by influencing the activation of the DUSP6-ERK1/2 pathway, which contributes to TAMs aggregation within NSCLC tumors to shape an immunosuppressive microenvironment. The HIV accessory protein viral protein-x (VPX) specifically degrades SAMHD1 to promote HIV replication. Similarly, the vpx-engineered oncolytic adenovirus (oAd-vpx) targets SAMDH1 degradation to enhance oncolytic adenovirus replication and weaken the hostile immune microenvironment shaped by TAMs, thereby triggering a CD8+T-cell-dependent antitumor immune response. The combination of oAd-vpx and αPD-1 inhibits tumor growth and enhances sensitivity to ICIs in both mouse and human NSCLC. CONCLUSIONS:This research identifies a key mechanism of SAMHD1-driven immunosuppression and highlights its important role in oncolytic adenovirus therapy. This study provides a theoretical basis for targeting SAMHD1 as a drug therapy strategy in patients with NSCLC.

Background Accurate metastasis prediction in lung adenocarcinoma is essential for effective treatment plans and improved prognosis. Current methods face challenges in accuracy and clinical application. Methods We developed a binary classification model (XGBoost) and a multiclassification model (stacking) using SEER database data. The binary model predicts metastasis presence (M0 vs. non-M0), and the multiclassification model further refines the degree of metastasis (M1a, M1b, M1c). Model performance was assessed using ROC AUC, PR AUC, and KS curves. SHAP values were used to analyze important features and explain the decision-making process. Results The binary model achieved ROC AUC and PR AUC scores exceeding 0.77, with the KS curve showing high consistency in distinguishing between positive and negative samples. The multiclassification model also performed well, demonstrating stability and generalizability across different metastasis stages. Key predictive factors included AJCC stage, survival duration, tumor size, and treatment information. Conclusion This study improves the accuracy and clinical application of metastasis prediction in lung adenocarcinoma through interpretable machine learning models. The combination of binary and multiclassification models not only predicts metastasis presence but also details its extent, providing valuable clinical decision support. Future research should integrate diverse data sources to enhance model robustness and better serve clinical practice. Clinical trial number Not applicable.

INTRODUCTION:Trastuzumab deruxtecan (T-DXd) was approved in China in October 2024 for previously treated human epidermal growth factor receptor 2 (HER2)-mutant (HER2m) unresectable/metastatic non-small cell lung cancer (NSCLC), based on DESTINY-Lung02 and DESTINY-Lung05 primary results. Here, we report the DESTINY-Lung05 final analysis. METHODS:DESTINY-Lung05 (NCT05246514), an open-label, single-arm, multicenter, phase 2 study, investigated T-DXd (5.4 mg/kg once every 3 weeks) in patients from China with HER2m (locally or centrally confirmed activating HER2 exon 19/20 mutation) metastatic NSCLC with disease progression on/after ≥ 1 prior anticancer therapy. The primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 by independent central review (ICR). Secondary endpoints included progression-free survival (PFS) by ICR, overall survival (OS), and safety. RESULTS:As of November 4, 2024, 72 patients with HER2m NSCLC had received T-DXd 5.4 mg/kg; the median duration of follow-up was 20.2 months (range, 2-27). Confirmed ORR (ICR) was 56.9% (95% confidence interval [CI] 44.7-68.6). Median PFS (ICR) and OS were 9.9 months (95% CI 7.1-16.5) and 21.0 months (95% CI 17.5-not calculable), respectively. Grade ≥ 3 drug-related adverse events occurred in 40 (55.6%) patients. Adjudicated drug-related interstitial lung disease/pneumonitis events were observed in 9 (12.5%) patients (n = 8 grade 1/2; n = 1 grade 3). CONCLUSIONS:With extended follow-up, T-DXd continued to demonstrate clinically meaningful and durable antitumor activity in patients from China with pretreated HER2m metastatic NSCLC, with no new safety signals. Results affirm the use of T-DXd as a treatment option in China for this patient population.

Lung cancer patients resistant to EGFR-TKIs often demonstrate a decreased response to Pemetrexed. Therefore, it is urgent to explore the mechanisms of drug resistance and develop new strategies. We investigated the potential of milk-derived exosomes as drug carriers, focusing specifically on pemetrexed encapsulated in these exosomes. We isolated exosomes from milk and loaded them with pemetrexed through electroporation to form a drug delivery carrier named as mExoPEM. Then, we examined how mExoPEM exerts anti-tumor effects in Gefitinib-resistant lung cancer cells, as well as the molecular mechanisms involved. Gefitinib-resistant cells were insensitive to the cytotoxicity of pemetrexed, due to the drug reflux caused by the elevated P-glycoprotein. When co-cultured with mExoPEM, resistant cells demonstrated enhanced anti-tumor responses in vitro and in vivo. Moreover, mExoPEM facilitated cellular uptake via Caveolin-1 (CAV1)-mediated endocytosis, which was regulated by the PPARγ/CAV1 pathway. Notably, pioglitazone, a PPARγ agonist, augmented mExoPEM uptake and synergized with mExoPEM to inhibit the proliferation of resistant cells. In conclusion, our study presents a promising strategy to address pemetrexed resistance in GR lung cancer cells through the use of milk exosome as drug carriers. Moreover, we elucidate the molecular mechanism underlying pemetrexed resistance and its enhanced delivery via milk exosome-mediated endocytosis.

Importance The ASTRUM-005 phase 3 randomized clinical trial showed substantial survival benefit from adding serplulimab to chemotherapy for previously untreated extensive-stage small cell lung cancer (ES-SCLC). However, the long-term outcomes are unclear. Objective To investigate the efficacy, safety, patient-reported outcomes (PROs), and exploratory biomarker findings from ASTRUM-005 at an extended follow-up. Design, Setting, and Participants This international, double-blind, phase 3 randomized clinical trial enrolled patients from September 12, 2019, to April 27, 2021 in China, Russia, Ukraine, Poland, Turkey, and Georgia. Eligible patients had histologically or cytologically confirmed ES-SCLC with no prior systemic therapy. Patients were followed up through May 7, 2024, and the data analysis of this prespecified, secondary analysis lasted from August to September 2024. The median follow-up duration was 42.4 months (range, 0.2-55.2). Exposures Patients were randomized in a 2:1 ratio to receive intravenous serplulimab (4.5 mg/kg; serplulimab group) or placebo (placebo group), which was combined with up to 4 cycles of carboplatin and etoposide every 3 weeks. Main outcomes and measures The primary end point was overall survival (OS). Secondary end points included other efficacy end points, safety, and PROs. Results A total of 585 patients (median [range] age was 63 [28-76] years in the serplulimab group and 62 [31-83] years in the placebo group) with previously untreated ES-SCLC, and 389 (66.5%) were randomly assigned to the serplulimab group and 196 (33.5%) to the placebo group. Baseline characteristics were balanced across treatment groups. At data cutoff, 280 OS events (72.0%) in the serplulimab group and 166 (84.7%) in the placebo group were observed. Compared with the placebo group, the serplulimab group showed more favorable efficacy (median OS, 15.8 [95% CI, 13.9-17.4] vs 11.1 [95% CI, 10.0-12.4] months; hazard ratio, 0.60; 95% CI, 0.49-0.73; P < .001). The serplulimab group showed improved OS rates at 4 years compared with the placebo group (21.9% vs 7.2%). Grade 3 or higher serplulimab-related or placebo-related treatment-emergent adverse events occurred for 136 (35.0%) and 57 patients (29.1%) in the respective groups. A PRO analysis revealed consistent trends of improved overall health, dyspnea, and pain in both groups and faster recovery from alopecia in the serplulimab group. Conclusions and Relevance This secondary analysis of a randomized clinical trial demonstrated long-term benefit from adding serplulimab to chemotherapy for previously untreated patients with ES-SCLC, supporting this therapy as a first-line standard of care for this patient population. Trial Registration ClinicalTrials.gov Identifier: NCT04063163

Wound healing is a complex tissue repair process that occurs through a series of overlapping phases, regulated by various cell types and corresponding signaling molecules, including G-protein-coupled receptors (GPCRs). GPCRs are a large family of cell surface receptors that respond to a variety of external signals and significant targets in the design of novel drugs for a wide range of human diseases. They play vital roles throughout the different stages of wound healing. Specifically, GPCRs are essential for the recruitment of immune cells and the activation of signaling cascades related to epidermal cell proliferation and differentiation, including Hedgehog-GLI, Hippo-YAP1, and Wnt/β-catenin pathways. Modifying GPCR activity through agonists or antagonists can alter GPCR signaling pathways, potentially affecting immune cell infiltration, the production of inflammatory mediators, and wound healing rates. This review summarizes the fundamental mechanisms of GPCR signaling pathways in wound healing and highlights recent discoveries regarding the roles and functions of GPCRs in this process.

8546 Background: EGFR exon 20 insertion (20ins)-positive non-small-cell lung cancer (NSCLC) is a rare subtype with limited therapeutic options and poor prognosis. Becotarug plus osimertinib showed encouraging activity and acceptable safety in a phase 1 study (NCT04448379). To assess its efficacy in EGFR 20ins-positive NSCLC, a phase 2 single-arm trial (NCT05132777) was initiated. To provide a comparator, a multicenter retrospective real-world study (NCT05513664) was served as an external control arm. Methods: Eligible patients in the phase 2 study had unresectable stage IIIB–IV NSCLC with EGFR exon 20 insertion mutations and ≥1 prior platinum-based chemotherapy; those relapsing within six months after neoadjuvant or adjuvant chemotherapy were also eligible. The external control comprised a real-world cohort treated with osimertinib, matched 1:1 on age, sex, stage, ECOG PS, brain metastases, and number of prior systemic therapies. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) in the trial arm and real-world ORR in the control arm. Secondary endpoints included disease control rate (DCR), duration of response (DoR) and progression-free survival (PFS). Safety was evaluated by incidence and severity of adverse events. Results: Of the 126 and 96 patients enrolled in the trial and control arms, respectively, 112 and 91 patients met criteria for the pre-matching cohort. After 1:1 propensity-score matching, 158 patients (79 per arm) comprised the post-matching population. Baseline characteristics were well balanced between arms, with 62.0% and 60.8% of patients, respectively, having received ≤1 prior line of systemic therapy. The IRC-assessed ORR was 46.8% (95% CI, 36.24–57.73) in the trial arm versus 7.6% (95% CI, 3.53–15.60) in the control arm. Notably, the lower bound of the trial-arm 95% CI (36.24%) exceeded the control-arm point estimate (7.6%). The absolute ORR difference was 39.2% (95% CI, 25.96–50.87; P < 0.0001), corresponding to an odds ratio of 10.72 (95% CI, 4.18–27.51). Furthermore, in a propensity score–matched analysis restricted to patients receiving osimertinib monotherapy (64 per arm), the combination therapy produced a greater ORR (42.2% [95% CI, 27.5-54.8], P < 0.0001). Higher DCR were achieved in trial arm compared to control arm (77.2% [95% CI, 66.8-85.1] vs 64.6% [95% CI, 53.6-74.2], P = 0.080). The median PFS in trial arm was significantly longer than that in control arm (6.9 vs. 4.8 months, P = 0.007). Other efficacy endpoints showed consistent trends favoring the combination therapy. The most common adverse events were EGFR-related mucocutaneous toxicities in both arms. Conclusions: This study further supports the efficacy and tolerability of becotarug plus osimertinib in patients with platinum-refractory, EGFR 20ins-positive NSCLC. Clinical trial information: NCT05513664 ; NCT05132777 .

Background: ASTRUM-002 met the primary endpoint of progression-free survival (PFS) with the combination of serplulimab plus HLX04 (bevacizumab biosimilar) and chemotherapy at interim analysis. Here, we report the results of the final survival analysis. Methods: A total of 636 patients with treatment-naïve, locally advanced or metastatic nonsquamous non-small cell lung cancer (nsq-NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)/ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) genetic alterations were randomized 1:1:1 to receive serplulimab plus HLX04 and chemotherapy (group A), serplulimab plus HLX04 placebo and chemotherapy (group B), or double placebo plus chemotherapy (group C). Patients and the investigators were blinded to the group assignments. The primary endpoint was blinded independent central review-assessed PFS. Overall survival (OS) was the key secondary endpoint. Results: At the final analysis, median OS was 23.7 (95% confidence interval [CI] 20.5 to 27.5) months, 26.8 (95% CI 21.2 to 30.9) months, and 20.3 (95% CI 16.2 to 24.6) months in groups A (n = 212), B (n = 214), and C (n = 210), respectively. A significant reduction in risk of death for group B compared to group C was observed (hazard ratio [HR] = 0.66, 95% CI 0.52 to 0.83; P < 0.001). A total of 79 (37.6%) patients in group C had crossed over to serplulimab plus HLX04 treatment. Median OS in group C adjusted by the 2-stage model was 14.2 months (95% CI 11.9 to 17.0), corresponding to an adjusted HR of 0.53 (95% CI 0.42 to 0.68; P < 0.001) for group B versus group C. Using the rank-preserving structural failure time model, the adjusted median OS in group C was 17.9 months (95% CI 14.2 to 20.3), with a corresponding adjusted HR of 0.65 (95% CI 0.51 to 0.83; P < 0.001). No statistical difference in median OS for group A compared to group B (HR = 1.12, 95% CI 0.88 to 1.42; P = 0.363) was found. Conclusions: Serplulimab plus chemotherapy significantly prolonged OS and maintained PFS benefit compared to chemotherapy; however, the addition of bevacizumab biosimilar HLX04 did not yield further improvement for the first-line treatment of nsq-NSCLC without EGFR or ALK/ROS1 genetic alterations. Trial registration: This trial was registered at ClinicalTrials.gov (NCT03952403, date of registration: 2019 May 14).

Colorectal cancer peritoneal metastasis (CRC-PM) often has poor prognosis after traditional hyperthermic intraperitoneal chemotherapy (HIPEC) due to constraints of respiratory movements, intestinal peristalsis and peritoneum plasma barrier. Herein, cisplatin and 17AAG were loaded into a thermoresponsive biodegradable polyurethane (PU) hydrogel, forming the CDDP/17AAG@PU system. This system showed favorable in vitro sustained release properties, controllable thermosensitive gelation at 43°C and excellent biocompatibility. Benefiting from the hydrogel's sustained release at safe doses, compared with the free drug group, this system significantly reduced serum biochemical abnormalities, as indicated by lower serum ALT/CREA levels and less apoptosis of normal intestinal cells. Moreover, its thermosensitive treatment enhanced antitumor efficacy by promoting DNA cross-linking and inhibiting oncogenic signaling-related proteins (p-PI3K, p-AKT, MMP2). In vivo experiments showed it more effectively inhibited CRC-PM compared to single-drug treatment and the control group. In conclusion, the safe, degradable CDDP/17AAG@PU system spreads to cover CRC-PM tumors at 37°C and gels rapidly at 43°C (clinical HIPEC temperature). It reduces antitumor drug induced hepatorenal toxicity, exerts good efficacy against CRC-PM and thus hold considerable potential for clinical translation.

BACKGROUND:This study investigated molecular testing, treatment patterns, and prognosis in Chinese patients who progressed from first-line (1 L), epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs) therapy, highlighting limited real-world data on clinical practice. METHODS:Consecutive eligible patients were prospectively enrolled in 16-centers in China. The primary endpoints were second-line (2 L) treatment patterns and clinical outcomes, including median progression-free survival (mPFS) and median overall survival (mOS) from 2 L treatment. RESULTS:Overall, 300 patients were enrolled in the study, and among them, 291 patients were included in the Full Analysis Set, and 213(73.2%) underwent molecular testing, after progression from 1 L therapy. 30.5% (65/213) had tissue samples, while 66.7% (142/213) had plasma samples. In tissue and plasma samples, T790M positive rates were 53.8% and 43.7%, respectively. mPFS and mOS for patients with T790M positive who received third generation (3 G) EGFR-TKIs as 2 L therapy were 14.7 months and 32.0 months, respectively. The mPFS for patients with T790M negative who received 3 G EGFR-TKIs, prior EGFR-TKIs plus local therapy, and chemotherapy as 2 L therapy were 7.6 months, 10.2 months, and 4.9 months, respectively. The corresponding mOS for these patients were 21.2 months, 16.6 months, and 15.0 months, respectively. No new safety signal emerged. CONCLUSIONS:Patients with acquired resistance to first generation (1 G)/second generation (2 G) EGFR-TKIs receiving 3 G EGFR-TKIs, especially T790M positive, showed better clinical outcomes after molecular testing. CLINICAL TRIAL REGISTRATION:The study has been registered at ClinicalTrials.gov (NCT04207775).

With the increasing incidence of breast cancer globally, there is an urgent demand for enhanced diagnostic and therapeutic strategies. This comprehensive review explores advancements in fluorescent probe technology for breast cancer imaging and early diagnosis. Fluorescent probes offer unparalleled sensitivity and specificity in detecting cancer biomarkers, enabling early diagnosis and delineation of tumor margins during surgery. We categorize these probes into molecular, nano, ratiometric, the second near-infrared window (NIR-II), and multifunctional varieties, each with unique capabilities for targeting specific cancer markers. This review highlights recent innovations in probe design, emphasizing their applications in pathogenesis studies, drug development, precision medicine, and fluorescence-guided surgery. Despite their promising clinical potential, challenges such as safety, biomarker targeting accuracy, system compatibility, and clinical translation persist. Addressing these hurdles is crucial for the integration of fluorescent probes into standard cancer care, aiming to improve treatment outcomes and patient quality of life.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase II LOTIS-2 study. In the China bridging pivotal phase II OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥2 lines of systemic therapies were enrolled and treated every 3 weeks with 150 μg/kg Lonca for two cycles; then 75 μg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by an independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data cutoff, 64 patients received Lonca (median 4.0 cycles; range, 1-17). The median number of prior lines of therapies was 3.0 (range, 2-12). The ORR was 51.6% (95% confidence interval [CI]: 38.7-64.2), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) grade ≥3 treatment-emergent adverse events (TEAE), in which increased γ-glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAE were reported in 35 of 64 patients with four fatal TEAE. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

Oncolytic virotherapy represents a highly promising in situ antitumor vaccine, using natural or engineered oncolytic viruses to specifically target and eradicate tumors. Malignant tumors overexpress the surface protein CD24, which signals "don't eat me" to inhibit macrophage phagocytosis of tumor cells. Oncolytic viruses are designed to express CD24 inhibitors to augment tumor elimination, serving as a potential antitumor vaccine for cancer immunotherapy. Therefore, we have developed an engineered oncolytic adenovirus that incorporates interfering RNA targeting CD24 for silencing (oAd-shCD24). The oAd-shCD24 vaccine induces sustained tumor suppression and long-term survival in tumor-bearing mice across various tumor models by inhibiting CD24 expression. Mechanistic analysis demonstrates that oAd-shCD24 increases the quantity of tumor-infiltrating immune cells that possess an activated immune phenotype while reducing the proportion of immunosuppressive cells, thus reshaping the tumor immune microenvironment. The combination of oAd-shCD24 with PD1 inhibitors shows superior antitumor efficacy. In summary, the oAd-shCD24 tumor vaccine exhibits effective antitumor efficacy and may represent a potential antitumor therapeutic agent.

Malignant pleural effusion (MPE), persistently generated by thorax tumor cells at the advanced stage, remains a major challenge for cancer therapy. Herein, we develop an ultra-sensitive piezoelectric nano-system by doping ytterbium in metal-organic framework (O3P@LPYU), which can be triggered by physiological intrapleural pressure during breath. Under the gently alterative pressure, the piezoelectric nanoparticles with notable peroxidase-like activity effectively produce a burst of reactive oxygen species and induce immunogenic cell death by catalysis of carried ozone as well as peroxide in interstitial fluid. A clear and sustained biodistribution is observed in thorax effusion and tumors upon intrapleural administration of particle. Remarkably, due to the abundant substrates in oxygen-rich environment of pleural cavity, O3P@LPYU particle provides a potent reduction of MPE volume and durable inhibition of tumor growth in thorax. Our work not only develops a bio-responsive piezoelectric nano-system, but also provides a strategy for persistent suppression of MPE in clinics.

In clinical practice, patients with unresectable stage III non‐small cell lung cancer (NSCLC) often exhibit limited tolerance to concurrent chemoradiotherapy (cCRT). This retrospective study evaluated the efficacy and safety of induction chemoimmunotherapy followed by definitive radiotherapy (RT) and consolidation immunotherapy, compared with standard cCRT plus consolidation immunotherapy. A total of 102 patients treated at West China Hospital between June 2019 and June 2024 were analyzed. Primary endpoints were overall survival (OS) and progression‐free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment‐related adverse events (TRAEs). Survival outcomes were comparable between groups (median OS: not reached vs. 36 months, p = 0.52; median PFS: 25 vs. 28 months, p = 0.71), with higher 3‐year OS observed in the induction group (61.4% vs. 38.3%). In the induction group, ORR after systemic therapy was 74.2%, and post‐RT DCR reached 83.3%. TRAEs were comparable across groups, with pneumonitis being the most frequent toxicity and no significant increase in grade ≥3 events observed. These findings support the induction‐based sequential strategy as a viable alternative to cCRT for patients with unresectable stage III NSCLC, especially those unsuitable for concurrent treatment.

The EGFR-TKIs (epidermal growth factor receptor-tyrosine kinases inhibitors) offer significant benefits to lung cancer patients with sensitive EGFR mutations; however, the development of acquired resistance poses a significant challenge and leads to poor prognosis. Thus, exploring novel therapeutic strategies to overcome EGFR-TKI resistance is urgently needed. This study introduces an innovative approach utilizing folic acid-modified milk exosomes loaded with c-kit siRNA (FA-mExo-siRNA-c-kit) to target EGFR-TKI resistance in lung cancer. Initially, gefitinib-resistant lung cancer cells exhibited stemness characteristics, including an epithelial-to-mesenchymal transition phenotype and elevated ABCG2 expression, which were closely regulated by c-kit. Subsequent treatment with FA-mExo-siRNA-c-kit demonstrated effective suppression of c-kit expression and attenuation of stemness traits in vitro, reducing gefitinib resistance. In xenograft and liver metastasis models, sequential administration of FA-mExo-siRNA-c-kit and gefitinib resulted in decreased tumor growth and prolonged survival. Mechanistically, c-kit was found to regulate the AKT/mTOR/4EBP1/eIF4E axis, promoting stemness and gefitinib resistance in lung cancer cells. This study unveils a novel mechanism of EGFR-TKI resistance involving the c-kit/mTOR pathway and proposes a promising therapeutic strategy for EGFR-TKI-resistant lung cancer, particularly with liver metastasis, using FA-mExo-siRNA-c-kit, suggesting potential for improved patient outcomes and warranting further investigation.