Platinum-based chemotherapy left hundreds of mutations in the liver cells of children treated for hepatoblastoma, an average of 2,200 per liver sample, a mutation burden usually seen in adult livers. Mutation load rose with platinum exposure: children given cisplatin alone had fewer mutations than those given both cisplatin and carboplatin. Liver cells showed far more mutations than blood cells despite systemic treatment, and the authors argue these children need lifelong monitoring for secondary tumors and liver disease.
Why it matters: Quantifies mutational damage in healthy childhood tissue from standard platinum therapy and sets an agenda for lifelong survivorship monitoring.
Antibody-coated lipid nanoparticles targeting TREM2 on tumor-associated macrophages delivered mRNA encoding CXCL9 together with a Toll-like receptor agonist, reversing immunosuppression and increasing tumor infiltration and activity of cytotoxic T lymphocytes. Adding PD-L1 and CTLA-4 checkpoint inhibitors produced a CTL-favoring immunological environment and durable memory immunity, supporting TAM reprogramming as a route to better immunotherapy response.
ELF integrates five pretrained pathology foundation models into unified slide-level representations, trained on 53,699 whole-slide images across 20 anatomical sites. It outperformed its constituent and slide-level foundation models on disease classification, biomarker detection, and anticancer and immunotherapy response prediction across multiple cancer types. Its architecture allows data-efficient downstream evaluation, including settings with limited data such as therapeutic response prediction.
An industrialized surface protein proximity-mapping workflow produced 248 proximity maps across 12 receptor tyrosine kinases and 28 tumour cell systems, yielding MetaMap, a framework that defines spatial protein communities and the concept of tumour-associated proximity antigens (TAPAs). Applied within a multimodal prioritization framework, it identified EGFR-CDCP1 as a TAA-TAPA pair that enhances tumour cell killing across therapeutic modalities, making disease-specific membrane proximity a design principle for precision multispecific therapeutics.
Integrated mutational footprints (IMFs), built by combining single-base substitution, indel, copy-number and six novel complex structural variant signatures, explain the mutational processes in 85% of primary prostate cancer genomes across 959 donors from the Pan Prostate Cancer Group. Four IMFs, present in 37% of primary tumours, were linked to shorter time to metastasis, and IMFs predicted sensitivity to androgen receptor pathway inhibitors in metastatic disease, supporting their use in risk stratification and treatment selection.
Adding atezolizumab to neoadjuvant taxane-carboplatin-anthracycline chemotherapy did not significantly improve event-free survival in stage II-III triple-negative breast cancer, with an HR of 0.80 (95% CI, 0.62-1.03; P = 0.083) and a 4-year EFS difference of 3.3%. Prespecified subgroup analysis suggested benefit in patients with clinical lymph node involvement (P interaction = 0.039), and an exploratory mRNA subset analysis pointed to basal-like immune-activated tumors as potential responders. Immune-related adverse events occurred in 27.6% with atezolizumab versus 11.4% with placebo.
The FDA approved Replimune's oncolytic immunotherapy Tudriqev (vusolimogene oderparepvec), formerly RP1, in August for unresectable advanced melanoma that has progressed after PD-1 immunotherapy. The engineered HSV-1 virus encodes GM-CSF and the fusogenic GALV-GP-R glycoprotein to spread through tumours. It is the second oncolytic virus approved, after Amgen's Imlygic (talimogene laherparepvec).
COVID-19 mRNA vaccination before or after starting immune checkpoint inhibitors was associated with modest early overall survival gains in a nationwide population-based cohort of patients with cancer, concentrated in the first few months after ICI start. Similar survival patterns seen with other vaccines suggest non-specific effects rather than a vaccine-specific benefit.
A single-cell spatial transcriptomic atlas of metastatic breast cancer profiles 520,850 cells from 126 tumor samples of 44 patients, covering 171,766 cancer cells and 349,084 tumor microenvironment cells across primary and metastatic lesions. Multiple time points per patient revealed treatment-induced transcriptional changes driving therapy resistance, immune subpopulations predictive of hormone receptor loss, and transcriptomic features of subclones selected during progression that hold future metastatic potential.
Why it matters: It provides a large longitudinal spatial single-cell resource for studying metastatic breast cancer progression and therapy resistance.
ELF, a framework that ensembles five pathology foundation models into unified whole-slide image representations, outperforms any individual foundation model at disease classification, biomarker detection, and prediction of response to chemotherapy, targeted therapy, and immunotherapy. It was trained on nearly 54,000 slides spanning 20 anatomical sites.
An ensemble approach integrating five pretrained pathology foundation models into a single slide-level representation improves tumor subtyping, biomarker prediction, and therapy-response prediction. The gains come from exploiting complementary information across the five models, reported by Luo et al. in Cancer Cell. It points computational pathology toward ensemble and multimodal methods rather than single-model pipelines.
BrainChild Bio Inc. of Seattle and Cambridge, Mass., raised $116 million in series A financing backed by Seattle Children's Research Institute and WRF Capital, with an undisclosed family fund leading. The company delivers CAR T cells directly into the cerebrospinal fluid rather than the bloodstream, aiming to allow repeat dosing for CNS cancers while avoiding systemic toxicities seen in other CAR T programs. Targets include B7-H3, EGFR and IL-13RA2.
Ivonescimab, from Akeso and Summit, cut the risk of death by 27% versus Keytruda in the phase 3 Harmoni-2 trial, which tested the drug as first-line treatment for PD-L1-positive non-small cell lung cancer. The survival benefit was especially pronounced in patients with high PD-L1 expression, strengthening the case for a challenger to pembrolizumab in this setting.
The FDA has approved Bayer's tyrosine kinase inhibitor Hyrnuo for first-line treatment of patients with HER2-mutant non-small cell lung cancer. The approval comes roughly half a year after the FDA cleared Boehringer Ingelheim's rival TKI Hernexeos for a similar setting. The two drugs now compete in the same indication.
AstraZeneca's camizestrant, combined with a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), received FDA accelerated approval on September 4 for adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer who developed ESR1 mutations during aromatase inhibitor and CDK4/6 inhibitor treatment. The FDA also approved a companion diagnostic that detects emerging ESR1 resistance mutations in circulating tumor DNA. The approval rests on the pivotal Phase III SERENA-6 trial.
Why it matters: FDA accelerated approval of AstraZeneca's camizestrant plus CDK4/6 inhibition for ESR1-mutant breast cancer, with a ctDNA companion diagnostic.
A multi-omics study led by Fan Jia's team at Zhongshan Hospital, published in Science, used Stereo-seq, single-cell and chromatin accessibility data to identify two key events in liver cancer metastatic colonization: disseminated tumor cells with high Phgdh expression establish an immune-desert niche in a quiescent state, and Cx3cr1-positive macrophages later drive metastatic reactivation. PHGDH-positive tumor cell features were cross-validated in public single-cell datasets from lung adenocarcinoma and ovarian cancer.
CDK4/6 inhibition redistributes hypophosphorylated Rb to promoters and enhancers, where it not only represses cell cycle genes but also promotes expression of oestrogen-responsive genes by joining ER-rich transcriptional hubs, partly through KDM5A. This Rb-driven ER transcriptional program is pro-proliferative: anti-oestrogen therapy neutralizes it in endocrine-sensitive tumours, but it persists in ESR1-mutant breast cancer and limits CDK4/6 inhibitor efficacy. The work reframes Rb as a dual-function transcriptional regulator.
A kinetic assembly method encapsulates the NIR-II dye DQP and protein in polymers, tuning the dye's aggregated state so monomers carry NIR-II fluorescence while aggregates drive photothermal conversion under single-wavelength excitation. The aggregated state's π-π stacking produces heat that triggers charge reduction and size enlargement of DQPNPs, increasing intracellular tumor retention in orthotopic hepatoma and improving both fluorescence intensity and photothermal efficacy. The work decouples imaging from therapy within one dye platform, easing the fluorescence quenching problem of conventional photothermal nanotheranostics.
Sintilimab can trigger cystitis/ureteritis that mimics infection, a 44-year-old woman with high-grade endometrial stromal sarcoma shows. After three cycles of sintilimab with nab-paclitaxel and carboplatin she developed severe urinary frequency, urgency and dysuria unresponsive to empirical antibiotics; methylprednisolone, with later piperacillin-tazobactam for cultured Enterococcus faecalis, resolved symptoms. Rechallenge caused only mild symptoms and a switch to tislelizumab brought no recurrence. The report pairs the case with a structured literature review for managing such urological irAEs.
UniCure, a multi-modal foundation model, predicts drug-induced transcriptomic responses across diverse cellular contexts. It bridges cancer cell line data with patient-derived models to support personalized drug prioritization and patient stratification, and its predicted therapeutic rankings correlate strongly with clinical survival outcomes in real-world cohorts.
