Oncology[JOURNAL]
Sun
200 papers
Development and validation of artificial intelligence-assisted volumetric response criteria in pleural mesothelioma (ARTIMES): a retrospective, multicohort, multicentre study.
Lipman KBWG, Wittenberg R, de Oliveira Taveira M … +31 more , Smesseim I, Schmitz AMT, Boellaard TN, Chupetlovska K, Abdelatty MA, Petrychenko L, Jain N, Arico FM, Pugliese V, Cornelissen R, Mulders TA, Zwierenga F, Hiddinga BI, Shenouda M, Armato SG, Popat S, Peters S, Roux S, Zellweger C, Fontecedro AC, Frauenfelder T, Nguyen-Kim TDL, Beets-Tan RGH, Baas P, Dungey M, Bajaj A, Fennell D, Tissier R, Burgers JA, de Gooijer CJ, Trebeschi S
Lancet Oncol · 2026 Jul · PMID 42309108 · Publisher ↗
BACKGROUND: Response evaluation in pleural mesothelioma is challenging because its crescent growth pattern is poorly captured by diameter-based criteria. We aimed to develop and validate artificial intelligence (AI)-assi...
BACKGROUND: Response evaluation in pleural mesothelioma is challenging because its crescent growth pattern is poorly captured by diameter-based criteria. We aimed to develop and validate artificial intelligence (AI)-assisted volumetric response criteria (ARTIMES) based on automated tumour segmentation and biologically derived thresholds. METHODS: In this retrospective, multicentre study, we included 10 926 CT scans from 2080 patients from 14 cohorts. A subset totalling 1176 CT scans from routine care (Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital) and trial cohorts (INITIATE, NivoMes, PEMMELA, LUME-MESO, NVALT19, and MiST1 trials) was annotated by 12 radiologists and 1 pulmonologist, supplemented by 100 negative CT scans, to train a deep-learning segmentation model. Internal testing included 98 CT scans from independent international hospitals in LUME-MESO. External testing included data from the MEDUSA cohort (101 CT scans with radiologist-corrected segmentations) and two fully independent manual segmentation datasets from SAKK17/18 (22 CT scans) and the University of Chicago (15 CT scans). AI segmentations were evaluated through dice similarity coefficient (DSC) and normalised surface distance (NSD) at 3 mm. Progressive disease thresholds were derived using data from patients with multiple CT scans before first-line therapy or receiving only supportive care after first-line treatment (611 CT scans), and partial response thresholds from inter-reader variability (derived from 451 CT scans). ARTIMES was validated using data from eight clinical trials (4674 CT scans; 943 patients) and compared with modified Response Evaluation Criteria in Solid Tumors (mRECIST) using time-varying Cox proportional hazards models and trial-level surrogate endpoint analysis against overall survival using R and surrogate threshold effect. FINDINGS: DSC was 94-95% in internal testing and 71-80% with manual segmentations. NSD was 98% and 81-93%, respectively. ARTIMES demonstrated superior patient-level prognostic performance compared with mRECIST (concordance index 0·83 [95% CI 0·79-0·87] vs 0·73 [0·66-0·80]; p=0·023) and detected progression a median of 5 weeks earlier (124 days [95% CI 115-126] vs 162 days [138-167]; p<0·0001). At the trial level, ARTIMES-based progression-free survival showed stronger correlation with overall survival (R 88% [95% CI 42-100]) than did mRECIST-based progression-free survival (R 6% [0-97]) and demonstrated a surrogate threshold effect at a progression-free survival hazard ratio of less than 0·82; no threshold was observed for mRECIST. Baseline AI-derived tumour volume independently predicted overall survival and outperformed T stage and WHO performance status. INTERPRETATION: ARTIMES-based progression-free survival improves prognostic stratification and shows better trial-level surrogacy for overall survival compared with mRECIST-based progression-free survival. Pending prospective validation, ARTIMES could potentially facilitate a more reliable response evaluation in pleural mesothelioma. FUNDING: Asbestos-Related Disease Section (SAGA) of the Dutch Society of Pulmonology and Tuberculosis (NVALT), Dutch Cancer Society, and Dutch Ministry of Health, Welfare and Sport.
Targeting SMYD2 improves immunotherapy response in experimental hepatocellular carcinoma.
Bueloni B, Fusco M, Fiore E … +12 more , Malvicini M, Cantero MJ, Lameroli L, Casadei M, Ruiz BM, Mercogliano F, Santamaría E, Atorrasagasti C, Argemi J, Canbay A, Bayo J, Mazzolini G
Mol Ther Oncol · 2026 Jun · PMID 42306568 · Full text
Therapeutic options for hepatocellular carcinoma (HCC) remain scarce and limited by resistance, underscoring the need for novel approaches. The lysine methyltransferase SMYD2 is overexpressed in several cancers and regul...
Therapeutic options for hepatocellular carcinoma (HCC) remain scarce and limited by resistance, underscoring the need for novel approaches. The lysine methyltransferase SMYD2 is overexpressed in several cancers and regulates oncogenic signaling through histone and non-histone substrates. However, its role in HCC is incompletely defined. We integrated transcriptomic analyses of patient samples with assays and orthotopic murine models to evaluate the therapeutic potential of SMYD2 inhibition in HCC. was enriched in intratumoral regions and associated with immunosuppressive and Wnt/β-catenin-driven programs. , SMYD2 pharmacological inhibition with AZ-505 reduced tumor burden and induced pro-inflammatory transcriptional changes. The antitumor activity of AZ-505 was also evident in Wnt/β-catenin-active tumors, which further displayed reduced expression of proliferative and immunosuppressive signatures. , SMYD2 inhibition decreased tumor-cell Wnt ligand transcription and shifted macrophage responses toward reduced expression, in a pattern consistent with reduced Wnt/β-catenin-associated signaling. Finally, AZ-505 synergized with anti-PD-1 in Wnt/β-catenin-active tumors, expanding cytotoxic T cell and antigen-presenting populations. Transcriptomic analyses of combination-treated tumors showed suppression of Wnt/β-catenin- and TGF-β-pathway-associated signatures alongside activation of immune-stimulatory responses. These results position SMYD2 as a dual regulator of tumor growth and immune suppression, and as a promising target to overcome ICI resistance in HCC.
Endothelial injury is a central driver of systemic IFN-β toxicity and is reversible through Jak inhibition.
Zhang L, Pham L, Steele MB … +4 more , Jenks N, Nace R, Russell SJ, Peng KW
Mol Ther Oncol · 2026 Jun · PMID 42306567 · Full text
Oncolytic viruses (OVs) encoding interferon beta (IFN-β) are under clinical evaluation. IFN-β is an attractive transgene due to its antiproliferative and immunomodulatory properties; however, the systemic effects of sust...
Oncolytic viruses (OVs) encoding interferon beta (IFN-β) are under clinical evaluation. IFN-β is an attractive transgene due to its antiproliferative and immunomodulatory properties; however, the systemic effects of sustained IFN-β expression remain poorly defined. Here, we demonstrate that prolonged circulating IFN-β induces dose-dependent toxicity in murine models. Persistent IFN-β exposure led to elevated transaminases, thrombocytopenia, lymphopenia, and reduced hemoglobin. Histopathologic analysis revealed sinusoidal endothelial sloughing, microvascular coagulation with microthrombi, and hepatocellular vacuolation and degeneration, along with bone marrow hemorrhage and cell death. These toxicities were absent in type I interferon receptor knockout mice. Importantly, termination of IFN-β production via inducible caspase-9 in adeno-associated vector-transduced cells reversed toxicity and normalized serum transaminases. In Balb/c mice bearing MPC-11 myeloma tumors which are highly permissive to IFN-β-expressing OVs, treatment induced rapid tumor lysis, elevated plasma IFN-β, and mortality. Importantly, co-administration of ruxolitinib, a clinically approved JAK1/2 inhibitor, dampened IFN-β signaling and rescued mice from lethal toxicity. Collectively, these findings define the pathophysiological consequences of sustained systemic IFN-β exposure and identify ruxolitinib as a potential mitigation strategy to manage IFN-β-mediated toxicity during OV treatment.
Impact of germline mutations on breast cancer: Susceptibility to DNA-damaging agents.
Jo S, Shim WC, Park S … +13 more , Kweon T, Ryu WJ, Hwang Y, Kim MW, Ahn JH, Lee YJ, Lee SH, Won D, Nam EJ, Han JW, Kim TI, Park JS, Park HS
Mol Ther Oncol · 2026 Jun · PMID 42306566 · Full text
Germline mutations in homologous recombination-related genes significantly increase the lifetime risk of breast, ovarian, and other cancers; thus, the concept of BRCAness has been extensively studied. In this study, we a...
Germline mutations in homologous recombination-related genes significantly increase the lifetime risk of breast, ovarian, and other cancers; thus, the concept of BRCAness has been extensively studied. In this study, we aimed to investigate the association between germline mutations and breast cancer in clinical and experimental settings. Germline pathogenic or likely pathogenic variants in were identified through multigene panel testing in the PLEASANT studies. Fourteen cases of breast cancer with germline pathogenic or likely pathogenic variants in were identified. Compared to 1,446 wild-type cases of breast cancer, they appeared to be more aggressive. The proportion of patients with triple-negative breast cancer (TNBC) was higher and larger tumors (>2 cm) were more common. RAD51D-deficient tumors showed better pathological complete responses, defined as ypT0 ypN0, to neoadjuvant chemotherapy. Based on clinical findings, we analyzed the impact of RAD51D-deficiency on drug sensitivity to identify targetable vulnerabilities in RAD51D-deficient tumors. These TNBC cells were significantly more sensitive to cisplatin than wild-type TNBC cells, consistent with our clinical data. In conclusion, RAD51D-deficient tumors were shown to have a phenotype similar to that of BRCA1-deficient tumors, and further investigation of responses to DNA-damaging agents, particularly platinum-based chemotherapy, is warranted.
Engineering potent TILs from an immune-excluded tumor: Insights from chondrosarcoma.
Al-Marayaty R, Pollack SM
Mol Ther Oncol · 2026 Jun · PMID 42306565 · Full text
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Unveiling the variations in penile cancer care: identifying knowledge gaps and research priorities.
Prakash G, Arora A, Basile G … +6 more , Mohanty S, Joshi A, Menon S, Shah H, Bandini M, Murthy V
BMJ Oncol · 2026 · PMID 42299326 · Full text
Penile cancer (PeCa) is a rare malignancy with substantial global variation in clinical presentation, staging practices and treatment approaches. This scoping review synthesises current evidence across key domains of PeC...
Penile cancer (PeCa) is a rare malignancy with substantial global variation in clinical presentation, staging practices and treatment approaches. This scoping review synthesises current evidence across key domains of PeCa management, including tumour classification, human papillomavirus (HPV) integration, organ preservation, nodal staging, systemic therapy and survivorship care. Despite recent updates in the American Joint Committee on Cancer staging system, limitations persist, particularly the absence of biologically relevant factors such as HPV status. While HPV-associated tumours may exhibit different responses to radiotherapy and systemic treatments, routine HPV testing and serotyping are not yet standardised in clinical practice. Early-stage PeCa remains amenable to organ-sparing approaches-including brachytherapy and reconstructive surgery-yet access to these modalities varies widely. Nodal management remains an area of controversy, with global inconsistencies in surgical templates and staging algorithms. Dynamic sentinel lymph node biopsy is emerging as a minimally invasive alternative but remains underused outside of high-volume centres. For node-positive disease, there is growing support for treatment intensification with chemotherapy and radiotherapy; however, prospective evidence is limited. Survivorship issues, particularly regarding psychosocial support and functional outcomes, remain poorly addressed in both research and routine care. This review identifies persistent gaps in the literature and highlights the need for international consensus-building, longitudinal data collection and equitable access to multidisciplinary care through collaborative efforts.
Correction for 'Impact of loneliness on cancer mortality: a systematic review and meta-analysis'.
BMJ Oncol · 2026 · PMID 42299325 · Full text
[This corrects the article DOI: 10.1136/bmjonc-2025-000840.].
[This corrects the article DOI: 10.1136/bmjonc-2025-000840.].
Aumolertinib with or without chemotherapy in EGFR-mutated advanced non-small-cell lung cancer (AENEAS2): an open-label, multicentre, randomised, controlled, phase 3 trial.
Li Z, Hu J, Chen J … +19 more , Yu Y, Meng X, Dong X, Hu Y, Ji Y, Liu H, Wang W, Ning F, Zhang Z, Liu C, Zhang Z, Wang Q, Zheng W, Wang H, Qu X, Chen Z, Fan S, Zhang X, Lu S
Lancet Oncol · 2026 Jul · PMID 42296979 · Publisher ↗
BACKGROUND: Although third-generation epidermal growth-factor receptor (EGFR)-tyrosine-kinase inhibitors (TKIs) are standard first-line therapies for patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC)...
BACKGROUND: Although third-generation epidermal growth-factor receptor (EGFR)-tyrosine-kinase inhibitors (TKIs) are standard first-line therapies for patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC), their effectiveness is often limited by the emergence of drug resistance and subsequent disease progression. Given the previously established clinical efficacy and adverse event profile of aumolertinib, we aimed to evaluate the efficacy and adverse event profile of aumolertinib in combination with platinum-based chemotherapy versus aumolertinib monotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC patients with EGFR-sensitive mutations. METHODS: The open-label, multicentre, randomised, controlled, phase 3 AENEAS2 trial was done across 60 hospitals in China. Patients aged at least 18 years with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; treatment-naive; histologically or cytologically confirmed locally advanced or metastatic NSCLC harbouring EGFR-sensitive mutations (ex19del/L858R with or without other EGFR mutations) were eligible. Brain metastases were allowed if neurologically stable. Previous EGFR-TKI therapy was an exclusion criterion. Patients were randomly assigned (1:1) with block randomisation (block size of 6), stratified by EGFR mutation type and baseline brain metastasis, to receive aumolertinib monotherapy (110 mg orally once a day) or combination therapy (aumolertinib 110 mg orally once a day plus pemetrexed 500 mg/m intravenously with cisplatin [75 mg/m] or carboplatin [area under the plasma concentration-time curve 5] intravenously on day 1 of 21-day cycles for 4-6 cycles), followed by maintenance therapy (aumolertinib 110 mg orally once a day and pemetrexed 500 mg/m intravenously once every 3 weeks). The primary endpoint was progression-free survival assessed by blinded independent central review (BICR; RECIST version 1.1). Efficacy was analysed in the full-analysis set, which included all randomly assigned patients, and safety was analysed in patients who received at least one dose of the actual trial treatment. The trial is registered at ClinicalTrials.gov, NCT04923906, and is ongoing, but closed to enrolment. FINDINGS: Between Aug 4, 2021, to June 18, 2024, of 1011 patients assessed for eligibility, 624 randomly assigned patients (median age 59·0 years [IQR 52·0-66·0]; 337 [54%] were female, 287 [46%] were male) were randomly assigned. 310 (50%) patients received combination therapy and 314 (50%) received monotherapy. As of the data cutoff date (June 18, 2024), the median follow-up was 23·4 months (IQR 20·5-26·5), In the full-analysis set, median BICR-assessed progression-free survival was 28·9 months (95% CI 26.3, NA) in the combination therapy versus 18·9 months (17·8-21·1) in the monotherapy (hazard ratio [HR] 0·47, 95% CI 0·37-0·60; log-rank p<0·0001). The most common grade 3-4 adverse events (occurring in at least 20% in any group) were neutrophil count decreased (168 [55%] of 304 in the combination group versus four [1%] of 316 in monotherapy group), white blood cell count decreased (103 [34%] vs one [<1%]), and platelet count decreased (62 [20%] vs two [1%]). Serious adverse events occurred in 109 (36%) patients in the combination group and 53 (17%) in the monotherapy group, the most common of which were platelet count decreased (22 [7%] vs 0), neutrophil count decreased (17 [6%] vs 0), white blood cell count decreased (13 [4%] vs 0), and anaemia (ten [3%] vs two [1%]). Treatment-related deaths occurred in one (<1%) patient in the combination group (encephalopathy) and two (1%) in the monotherapy group (pulmonary embolism and respiratory failure with circulatory collapse). INTERPRETATION: Aumolertinib in combination with chemotherapy significantly improved progression-free survival. Although this regimen was associated with increased toxicity, the side-effects were managed with dose adjustment and supportive treatment aligned with clinical practice. Long-term follow-up is required to assess overall survival. The AENEAS2 study provides evidence to guide clinical practice regarding EGFR-TKIs and their combination use in treating patients with advanced EGFR-mutated NSCLC. FUNDING: Jiangsu Hansoh Pharmaceutical Group, and the Collaborative Innovation Center for Clinical and Translational Science by Ministry of Education & Shanghai. TRANSLATIONS: For the Chinese translation of the abstract see Supplementary Materials section.
SF3A3 in Liver Hepatocellular Carcinoma: Oncogenic Role and Prognostic Significance.
Liu F, Blakeley PD
Oncology · 2026 Jun · PMID 42296035 · Publisher ↗
BACKGROUND: Splicing factor 3a subunit 3 (SF3A3) is a core component of the SF3A complex, which is essential for pre‑mRNA splicing. However, its role and prognostic significance in liver hepatocellular carcinoma (LIHC) r...
BACKGROUND: Splicing factor 3a subunit 3 (SF3A3) is a core component of the SF3A complex, which is essential for pre‑mRNA splicing. However, its role and prognostic significance in liver hepatocellular carcinoma (LIHC) remain poorly characterized. METHOD: We systematically investigated the role of SF3A3 in LIHC using RNA sequencing data, promoter methylation profiles, and proteomic data from The Cancer Genome Atlas (TCGA) and Genotype‑Tissue Expression (GTEx) datasets. Associations between SF3A3 expression and clinical or pathological features were analyzed, and the prognostic value of SF3A3 was assessed using survival analysis. RESULTS: SF3A3 mRNA and protein levels were elevated in LIHC tumors, whereas promoter methylation was reduced compared with matched normal liver tissues. High SF3A3 expression was positively associated with advanced tumor stage and grade, as well as TP53 mutation status. Elevated SF3A3 expression was linked to significantly poorer overall survival in patients with LIHC. SF3A3 expression showed a positive correlation with tumor‑associated fibroblast infiltration. Survival analyses indicated that SF3A3 expression level and tumor stage are key factors associated with LIHC overall survival. Gene set enrichment analysis (GSEA) revealed that tumors with high SF3A3 expression were significantly enriched for pathways related to the GABA‑A receptor complex and FGFR3 mutant receptor activity. CONCLUSIONS: The expression of SF3A3 in LIHC tumors is correlated with adverse pathological features and poor prognosis and potential biological mechanisms underlying the role of SF3A3 in LIHC were elucidated. This study highlights SF3A3 as a promising biomarker for prognosis and disease severity in LIHC. Keywords SF3A3, TCGA, GTEx, LIHC, tumor, prognosis, biomarker.
Magnetic Resonance Imaging Features as Predictors of Response and Prognosis Following Neoadjuvant Therapy in Rectal Cancer: A Retrospective Cohort Study.
Deng J, Cheng S, Li S … +1 more , Hou Y
Clin Med Insights Oncol · 2026 · PMID 42293813 · Full text
BACKGROUND: MRI-detected circumferential resection margin (CRM) involvement, extramural venous invasion (EMVI), and tumor deposits (TDs) are established high-risk features associated with poor prognosis in rectal cancer....
BACKGROUND: MRI-detected circumferential resection margin (CRM) involvement, extramural venous invasion (EMVI), and tumor deposits (TDs) are established high-risk features associated with poor prognosis in rectal cancer. These features may help identify patients who are more likely to benefit from neoadjuvant therapy (NAT). However, the prognostic significance of changes in these MRI high-risk features after NAT remains unclear. The objective of this study was to determine whether baseline MRI high-risk features can identify patients likely to benefit from NAT and whether their changes after NAT predict treatment response and prognosis in rectal cancer. METHODS: This retrospective single-center cohort study included patients who underwent curative resection for rectal adenocarcinoma and received neoadjuvant therapy (NAT) at Sun Yat-sen University, Sixth Affiliated Hospital, between 2017 and 2019. Patients with MRI-detected CRM involvement, EMVI, or TDs were classified as MRI high-risk. Those who showed a shift from MRI high-risk to MRI low-risk-defined by the absence of CRM involvement, EMVI, or TDs-on post-treatment scans were considered good responders. The survival outcomes of good responders were then compared to those of poor responders, who remained persistently MRI high-risk. Additional analyses were performed within the baseline MRI high-risk subgroup to determine which MRI high-risk features were most strongly associated with prognosis. RESULTS: The study included 302 patients in total. Of these, 146 (48.3%) were classified as MRI high-risk and 156 (51.7%) as MRI low-risk based on pre-treatment imaging. The high-risk group had significantly worse outcomes: three-year disease-free survival (DFS) was 54.8% compared with 93.6% in the low-risk group (p < 0.001), three-year overall survival (OS) was 76% versus 98.1% (p < 0.001), and the rate of local recurrence (LR) at three years was 10.9% compared to 1.3% (p = 0.002). Among the 146 patients initially identified as MRI high-risk, those who converted to low-risk status after treatment showed improved outcomes, with a three-year DFS of 82.9%, OS of 94.3%, and LR rate of 2.9%. Within the baseline MRI high-risk subgroup, baseline mrEMVI and mrTD, as well as post-treatment ymrMRF, ymrEMVI, and ymrTD, were associated with worse DFS. CONCLUSIONS: Baseline MRI high-risk features and their persistence after NAT were associated with poor prognosis in rectal cancer. MRI risk conversion after NAT may help identify a subgroup of initially high-risk patients with more favorable outcomes.
Rewriting microenvironment immunity in glioblastoma.
Figg JW, Flores CT
Mol Ther Oncol · 2026 Jun · PMID 42291139 · Full text
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Combined radiation and immunotherapy induces cytotoxic immunity that correlates with improved outcome in dogs with osteosarcoma.
Mason NJ, Gnanandarajah J, MaloneyHuss M … +8 more , Reetz J, Agnello KA, Gray F, Engiles J, Olenick L, Hart A, Thamm DH, Paterson Y
Mol Ther Oncol · 2026 Jun · PMID 42291138 · Full text
Ionizing radiation acts synergistically with immunotherapy by inducing immunogenic cell death and modulating the tumor microenvironment, promoting anti-tumor immune responses. In this pilot study, the safety and effectiv...
Ionizing radiation acts synergistically with immunotherapy by inducing immunogenic cell death and modulating the tumor microenvironment, promoting anti-tumor immune responses. In this pilot study, the safety and effectiveness of palliative radiation with a expressing (Lm-LLO-HER2), on delaying primary tumor progression in immunocompetent dogs with osteosarcoma was evaluated and correlative immune response biomarkers explored. Fifteen dogs with treatment naive, appendicular osteosarcoma, without evidence of metastatic disease received palliative radiation followed by Lm-LLO-HER2 immunotherapy every 3 weeks for an initial 8 doses then booster treatments. Treatment was well tolerated and delayed primary tumor progression and prolonged overall survival in 5/15 dogs. Peripheral blood mononuclear cell transcriptomic profiling revealed that baseline immune status and immune response to Lm-LLO-HER2 distinguished long-term from short-term survivors. Genes associated with Hedgehog signaling, senescence, DNA damage repair, and cell cycle were downregulated when compared to baseline in long-term survivors. These findings support further exploration of combination palliative radiation and -based immunotherapy in osteosarcoma and suggest that baseline immune status may determine clinical and immunological responses to combination therapy. Pet dogs with osteosarcoma represent a parallel population to pediatric osteosarcoma patients. These findings may inform future pediatric osteosarcoma clinical trials and patient stratification.
Innovative photodynamic therapy using rose bengal for the treatment of human melanoma.
Boileau M, Lefebvre A, Marhfor S … +7 more , Kali Mansouri M, Deleporte P, Paul Grolez G, Dewalle AS, Morales O, Delhem N, Mortier L
Mol Ther Oncol · 2026 Jun · PMID 42291137 · Full text
Rose Bengal (RB), a xanthene dye with established antitumor and immunomodulatory properties, is a cytotoxic molecule evaluated in human melanoma through phase 2 clinical trials. RB demonstrates intrinsic therapeutic acti...
Rose Bengal (RB), a xanthene dye with established antitumor and immunomodulatory properties, is a cytotoxic molecule evaluated in human melanoma through phase 2 clinical trials. RB demonstrates intrinsic therapeutic activity; however, its clinical application may be limited at high doses because of potential side effects, including photosensitivity. In this context, and given that RB also functions as a photosensitizer (PS), our objective was to enhance its efficacy by introducing a photodynamic therapy (PDT) approach using green light (550 nm) excitation. PDT relies on activation of a PS in the presence of oxygen, generating reactive oxygen species (ROS) that induce tumor cell death and stimulate immune responses. In terms of relative efficacy, PDT-RB was 121 and 40 times more effective than RB alone in HBL and LND melanoma cell lines, respectively. This reduced the RB concentration from 492 μM to 32 μM for HBL and from 1,043 μM to 74 μM for LND, achieving 80% cell death. This combination of light and low RB concentrations enhances ROS production and induces necrosis in metastatic melanoma cells. Moreover, PDT-RB preserves PBMC proliferation compared with high-dose RB, suggesting reduced immunotoxicity and potential immunogenic properties, supporting further investigation in more advanced models for future validation.
SIRPα ablated iPSC-derived macrophages resist hypophagia and enhance mAb-dependent and CAR-mediated cytotoxicity of solid tumors.
Smith PR, Kabir ME, Zhang J … +7 more , Maufort JP, Forsberg MH, Sedzro DM, Berres M, Thomson JA, Capitini CM, Slukvin II
Mol Ther Oncol · 2026 Jun · PMID 42291136 · Full text
The SIRPα-CD47 "don't eat me" checkpoint axis plays a critical role in shaping antitumor activities of macrophages within the tumor microenvironment (TME). However, targeting this axis with anti-CD47 antibodies to enhanc...
The SIRPα-CD47 "don't eat me" checkpoint axis plays a critical role in shaping antitumor activities of macrophages within the tumor microenvironment (TME). However, targeting this axis with anti-CD47 antibodies to enhance antitumor responses in clinical trials has been challenging. Here, we demonstrated that -knockout (KO) iPSC-derived macrophages (iMacs) exhibit superior antitumor activity against various CD47-expressing tumors when combined with cancer-targeted monoclonal antibodies (mAbs) or chimeric antigen receptors (CARs). Moreover, -KO protected macrophages from mAb- and CAR-driven hypophagia, enabling efficient tumoricidal effects even after serial tumor exposures. Retention of phagocytic activities in -KO iMacs was associated with heightened surface expression of Fc receptors and GD2-CAR compared to their -expressing counterparts. Despite the powerful impact of -KO on iMac antitumor activities , only modest efficacy was observed in human xenograft mouse models of SK-OV3 ovarian carcinoma and CHLA-163 neuroblastoma treated with mAb or CAR-iMac therapy, indicating further engineering or combinatorial therapeutic strategies are needed for potent antitumor efficacy. Together, these findings identify SIRPα as a regulator in macrophage hypophagia and underscore the advantages of using -KO macrophage therapeutic strategies to modulate the SIRPα-CD47 checkpoint to unleash macrophage antitumor activity within the TME.
Treatment-related adverse events of CD3-based T cell-engaging bispecific antibodies in patients with cancer: a meta-analysis of clinical trials.
Zhu Y, Liu K, Rosen ST … +2 more , Liu W, Zhu H
Lancet Oncol · 2026 Jul · PMID 42285121 · Publisher ↗
BACKGROUND: Clinical trials evaluating CD3-based T cell-engaging bispecific antibodies for cancer therapy have rapidly progressed from early investigations to clinical application. As these agents enter practice, it is e...
BACKGROUND: Clinical trials evaluating CD3-based T cell-engaging bispecific antibodies for cancer therapy have rapidly progressed from early investigations to clinical application. As these agents enter practice, it is essential to systematically characterise and summarise the range of treatment-related adverse events associated with these antibodies. METHODS: We conducted a meta-analysis by searching Cochrane, Embase, PubMed, and Web of Science for English-language clinical trials worldwide reporting treatment-related adverse events in patients receiving CD3-based T cell-engaging bispecific antibodies for cancer, published up to July 31, 2025. The primary outcomes were the overall incidence of treatment-related adverse events, and toxicity profiles (ie, the incidence of each specified adverse event, for both all-grade and grade 3 or worse treatment-related adverse events). Pooled overall incidence and profile estimates with 95% CIs for both all-grade and grade 3 or worse treatment-related adverse events were calculated using logit-transformed random-effects models. Heterogeneity across studies was quantified with the I statistic. The study is registered at PROSPERO (CRD420251130333). FINDINGS: A total of 104 clinical trials enrolling 10 353 patients (7311 with haematological malignancies and 3042 with solid tumours) were included. For haematological malignancies, the overall incidence of all-grade treatment-related adverse events was 97·5% (95% CI 95·2-98·7; I=88·2%), and 70·3% (62·6-77·0; I=94·4%) for grade 3 or worse adverse events. For solid tumours, corresponding incidences were 97·9% (95·7-99·0; I=57·0%) and 45·3% (38·4-52·4; I=87·0%), respectively. The most frequently observed all-grade treatment-related adverse events were cytokine release syndrome in haematological malignancies (43·3% [95% CI 33·9-53·1]) and solid tumours (46·3% [25·5-67·1]). The most frequent grade 3 or worse treatment-related adverse events were neutropenia (18·1% [11·1-26·9]) in haematological cancers and increased γ-glutamyltransferase (3·68% [0·86-6·98]) in solid tumours. Treatment-related deaths occurred in 94 of 9206 patients (1·0% [95% CI 0·8-1·3]; I=0·0%). The predominant causes were sepsis, pneumonia, neutropenic infection, respiratory failure, septic shock, and multi-organ failure. INTERPRETATION: The toxicity profile of T cell-engaging bispecific antibodies varies substantially across cancer types and antibody classes. This meta-analysis provides a comprehensive overview of treatment-related adverse event incidence and patterns, offering a valuable reference for optimising patient management in clinical practice. FUNDING: The National Natural Science Foundation of China and the Changsha Natural Science Foundation of Hunan Province of China.
Letter to the Editor.
Duenas-Gonzalez A
Oncology · 2026 Jun · PMID 42284269 · Publisher ↗
Abstract loading — click title to view on PubMed.
FLAG-Based Versus Standard 7+3 Induction Therapy in Adults with Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.
Abdulgayoom M, Aboukhalaf S, Osman M … +7 more , H Soliman N, Rahmoon SM, Rabadi M, Fituri N, Al-Mashdali AF, Kaddoura R, F Mohamed S
Oncology · 2026 Jun · PMID 42284251 · Publisher ↗
The standard induction regimen for newly diagnosed acute myeloid leukemia (AML) in eligible patients remains cytarabine-daunorubicin (7+3), although FLAG-based regimens are increasingly used in high-risk disease. We perf...
The standard induction regimen for newly diagnosed acute myeloid leukemia (AML) in eligible patients remains cytarabine-daunorubicin (7+3), although FLAG-based regimens are increasingly used in high-risk disease. We performed a PRISMA 2020-compliant systematic review and meta-analysis comparing FLAG-based induction with standard 7+3 in adults with newly diagnosed AML. Five retrospective cohort studies, including 534 patients, were analyzed. FLAG-based induction was associated with a significantly higher overall response rate than 7+3 (OR 1.83, 95% CI 1.03-3.22), without a significant difference in 30-day mortality (OR 0.56, 95% CI 0.12-2.69) or 60-day mortality (OR 0.79, 95% CI 0.29-2.14). Survival outcomes were heterogeneous and could not be pooled: median OS was similar in one cohort, whereas two studies reported improved OS with FLAG-based induction; DFS/RFS outcomes were inconsistently reported. FLAG-based induction was associated with higher receipt of consolidation therapy, while bridging to allogeneic transplantation did not differ significantly. Cytogenetic and molecular risk data were variably defined and incompletely reported, precluding reliable pooled subgroup analyses. Overall, FLAG-based induction improves response rates without a clear increase in early mortality or selected reported safety outcomes; however, its impact on survival remains uncertain and appears influenced by post-remission strategies. Prospective randomized trials are needed to better define its role in frontline AML therapy.
The Immunological Landscape of the Tumor Microenvironment: Implications for Immunotherapy of Unresectable and Metastatic Soft Tissue Sarcomas.
Zou S, Li A, Yang S … +6 more , Jin C, Zhu J, Xu J, Wang Y, Xue C, Wu M
Curr Treat Options Oncol · 2026 Jun · PMID 42283889 · Publisher ↗
The field of immunotherapy for unresectable soft tissue sarcomas (STS) is transitioning from a one-size-fits-all approach toward a precision immuno-oncology paradigm. The pronounced immunological heterogeneity among hist...
The field of immunotherapy for unresectable soft tissue sarcomas (STS) is transitioning from a one-size-fits-all approach toward a precision immuno-oncology paradigm. The pronounced immunological heterogeneity among histological subtypes and the limited predictive capacity of traditional classification underscore the imperative for immune-based stratification. Approximately 20% of STS exhibit an immune-activated tumor microenvironment, characterized by robust cytotoxic T lymphocyte infiltration, B-cell enrichment, and tertiary lymphoid structures (TLS); these patients demonstrate significantly higher objective response rates to immune checkpoint inhibitors (ICIs) and may be prioritized for such therapy. TLS status could be incorporated into routine clinical decision-making as a robust immunological biomarker for treatment selection. For the majority of patients with TLS-negative, immunologically "cold" tumors, however, single-agent ICIs are insufficient. Combination strategies designed to remodel the immunosuppressive tumor microenvironment represent a promising approach: enhancing tumor immunogenicity through epigenetic modulators, improving antigen presentation via CD47/SIRPα blockade, and exploring dual-checkpoint blockade to overcome T-cell exhaustion. For translocation-associated sarcomas, where neoantigen generation is inherently limited, adoptive cell therapies targeting specific antigens represent a particularly promising avenue. Biomarker-driven basket or umbrella trial designs are paramount to efficiently identifying optimal combination regimens and improving overall survival outcomes for patients with unresectable disease.
Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition.
Radic-Sarikas B, Markovic M, Zylka MM … +8 more , Sturtzel C, Ilg M, Surdez D, Metzelder M, Distel M, Ovsianikov A, Halbritter F, Kovar H
Mol Ther Oncol · 2026 Jun · PMID 42281954 · Full text
Bone sarcomas are rare and aggressive pediatric cancers with limited progress in targeted therapy development, partly due to the poor physiological relevance of conventional two-dimensional (2D) culture systems used for...
Bone sarcomas are rare and aggressive pediatric cancers with limited progress in targeted therapy development, partly due to the poor physiological relevance of conventional two-dimensional (2D) culture systems used for preclinical testing. To address this gap, we developed a standardized three-dimensional (3D) culture and drug-testing platform for Ewing sarcoma (ES) and osteosarcoma (OS) that more accurately recapitulates tumor biology. Notably, gene-expression analyses demonstrated that ES and OS spheroids transcriptionally converge toward patient tumor cell states, underscoring their physiological relevance for preclinical testing. Across 3D spheroids, bioprinted constructs, and patient-derived xenograft (PDX) cultures, we observed a consistent activation and dependency on the mevalonate pathway in ES. Leveraging this platform, we identified a selective therapeutic synergy between statins, which inhibit mevalonate pathway flux, and BCL-xL inhibitors-a vulnerability not detectable in 2D cultures. Importantly, this synergistic interaction was tumor-specific and absent in non-malignant fibroblasts, indicating a favorable therapeutic window. Together, these findings highlight the mevalonate pathway as a targetable metabolic dependency in ES and demonstrate how physiologically grounded 3D models can uncover clinically actionable treatment strategies that remain hidden in traditional 2D systems.
Treatment of oligometastatic lung cancers: new data, new drivers, new approaches.
O'Dwyer N, Palma DA
BMJ Oncol · 2026 · PMID 42281913 · Full text
The oligometastatic paradigm has expanded the use of stereotactic ablative radiotherapy (SABR) and local consolidative therapy (LCT) in metastatic non-small cell lung cancer (NSCLC), but accumulating evidence suggests th...
The oligometastatic paradigm has expanded the use of stereotactic ablative radiotherapy (SABR) and local consolidative therapy (LCT) in metastatic non-small cell lung cancer (NSCLC), but accumulating evidence suggests that 'oligometastatic NSCLC' is not a single clinical entity. As systemic therapy has advanced-particularly third-generation EGFR tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors-both the intent and the incremental value of local therapy have diverged by molecular subtype, metastatic tempo and treatment setting. In EGFR-mutated disease, multiple prospective studies now support LCT as a strategy to extend durable benefit from TKIs by ablating limited sites of disease, with contemporary randomised data emerging in the osimertinib era and ongoing trials addressing optimal timing and completeness of consolidation. In driver-negative, immunotherapy-treated NSCLC, early phase and real-world series suggest that carefully selected patients can achieve durable control within multimodality pathways, but the most practice-defining randomised evidence to date has not supported routine consolidation for all non-progressing patients and highlights pneumonitis risk, reinforcing the need for stringent staging and selection. Management of EGFR-mutated small and non-symptomatic brain metastases has similarly evolved towards systemic-first sequencing with selective stereotactic radiosurgery for high-risk lesions or focal central nervous system escape, informed by emerging randomised data. Across settings, lesion count alone is an imperfect surrogate for biology; metastatic tempo, molecular drivers and treatment response patterns are increasingly relevant to deciding when SABR should be comprehensive, selective or deferred. Ongoing trials in targeted and immunotherapy eras will determine when LCT should be integrated as standard care versus an optimisation strategy for a minority. We propose a pragmatic framework centred on treatment intent-comprehensive ablation for potentially curable limited disease versus focal ablation to maintain an effective systemic agent-aimed at supporting multidisciplinary decision-making as the evidence base evolves.
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