Tumor-derived LOXL4 stiffens the extracellular matrix in lung cancer, activating Piezo1 in CD8+ T cells and triggering Ca2+ influx with FAK1-YAP1 signaling that drives terminal exhaustion via YBX1, ACLY and KAT2A. Conditional knockout of Piezo1, Ybx1, Acly or Kat2a in murine CD8+ T cells abolished stiffness-induced exhaustion and suppressed tumor growth. Acetyldigoxin, identified by molecular docking as a high-affinity LOXL4 inhibitor among FDA-approved agents, softened the ECM, reversed CD8+ T cell exhaustion and synergized with anti-PD-1 blockade for durable tumor regression.
Roche's T-cell engager Lunsumio met its primary endpoint in a phase 3 confirmatory trial in earlier-line follicular lymphoma, adding another milestone for the company's T-cell engager portfolio.
China's NMPA approved on August 11, 2026 the combination of trastuzumab deruxtecan (T-DXd) with pertuzumab as first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer. The approval rests on the global DESTINY-Breast09 trial. The regimen challenges the long-standing escalation model in which patients start on trastuzumab plus pertuzumab with a taxane and switch to an ADC only after progression.
Bayer's sevapritinib received FDA accelerated approval as first-line treatment for adults with locally advanced or metastatic non-squamous non-small cell lung cancer harboring HER2 tyrosine kinase domain activating mutations. The approval extends the drug's use from its second-line approval in November 2025, allowing oral targeted therapy from diagnosis. In the SOHO-01 trial, the first-line cohort of 69 untreated patients showed a confirmed ORR of 75%, with 6% complete and 70% partial responses.
Chia Tai Tianqing's HER2 bispecific ADC TQB2102 has hit its prespecified primary endpoint and key secondary endpoints in the Phase III TQB2102-III-01 trial, per an interim analysis judged by an independent data monitoring committee. The trial tested the drug in HER2-low recurrent or metastatic breast cancer. The company says TQB2102 balances efficacy and safety through three core technical features.
The B7-H3-targeted antibody-drug conjugate Tam-Peli reduced the risk of death by 54% in patients with small cell lung cancer, according to findings presented at this year's World Conference on Lung Cancer. Tam-Peli is one of two B7-H3-directed ADCs for small cell lung cancer highlighted at the meeting, a cancer described as highly malignant, rapidly progressing and limited in treatment options.
The antiseizure drug levetiracetam is associated with longer survival and reduced tumor growth in diffuse midline glioma, but not in hemispheric high-grade glioma. In experimental models and patient cohort data, the effect arose from selectively dampening GABAergic synaptic signaling, acting independently of the drug's canonical SV2A-mediated antiseizure mechanism. This points to a tumor-specific therapeutic use for an already available drug.
A CRISPR/Cas9 knockout screen of immune checkpoint receptors in adapter CAR (AdCAR)-T cells identifies TIGIT disruption as a potent enhancer of cytotoxicity against AML. TIGIT knockout boosted AdCAR-T killing across five leukemia and lymphoma cell lines, whereas PD-1 disruption did not significantly improve killing of MOLM-13 wildtype cells. Pharmacological TIGIT blockade matched the knockout effect, and PD-1 blockade outperformed PD-1 gene disruption. The work points to the TIGIT-CD155 interaction as a key modulator of AdCAR-T function in AML.
Radiotherapy was found to drive a TET2-dependent epitranscriptomic program in myeloid cells that promotes differentiation into immunosuppressive M-MDSCs. Loss of TET2 preserved caRNA m5C-MBD6 signaling, restored IRF3-IFN-I activation, and generated myeloid-derived activating cells that strengthen radiotherapy-induced antitumor immunity. The work identifies a myeloid reprogramming strategy to potentiate radiotherapy and suppress metastasis.
Why it matters: It defines a targetable myeloid pathway that converts radiotherapy-induced immunosuppression into antitumor immunity and metastasis control.
A large language model-based resource, MSK-Tox, captured the incidence, timing, and grade of anti-cancer therapy toxicity across more than 50,000 patients. Analysis of six representative adverse events showed toxicity risk varies by cancer type, regimen, and clinical context, is predictable from pretreatment clinical features, and has two germline modes: an organ-intrinsic mode, exemplified by a regulatory variant near FOXE1 linked to hypothyroidism, and an immune-mediated mode in which HLA-DRB1*15 drives adrenal insufficiency after immune checkpoint inhibition. The work supports pretreatment risk assessment for harm on the same principles used to predict benefit.
A framework for interpreting cancer mutations maps significantly mutated regions onto protein domains and structural features, extending analysis beyond single genes and recurrent hotspots. The work by Hyeon et al., highlighted in Cancer Cell, establishes proteo-genomics as a way to assign biological and clinical meaning to somatic mutations across cancer genomes. It offers clinicians and researchers a structural lens for reading variants that gene-level interpretation misses.
Intra-cluster receptor density (IRD), measured by homo-FRET fluorescence anisotropy, acts as a molecular switch for TNFR1 signaling. Soluble TNF-α raises IRD at cluster cores and lowers it at rims; reducing IRD via membrane tension, zafirlukast, actin depolymerization, or cholesterol depletion suppresses sTNF-α signaling, while raising IRD by lowering membrane tension or a 3D gel-like microenvironment triggers ligand-independent activation. IRD may offer a route to modulating TNFR1 signaling.
On August 25, 2026, the FDA approved the HER2 bispecific antibody zanidatamab for first-line treatment of adults with unresectable locally advanced or metastatic HER2-positive gastric, gastroesophageal junction or esophageal adenocarcinoma confirmed by an FDA-approved test. One approval covers zanidatamab combined with tislelizumab plus fluoropyrimidine and platinum chemotherapy for patients with HER2-positive disease defined as IHC 3+ or IHC 2+/ISH+. The approvals were based on the HERIZON-GEA-01 study.
On September 14, 2026, Curium announced FDA full approval of Bexlutry (oxodtreotide), the first approved generic radioligand therapy, termed a "radioligand equivalent." It copies Novartis's Lutathera, an SSTR2-targeted radioligand therapy obtained through Novartis's acquisition of Advanced Accelerator Applications, first FDA-approved in 2018 for gastroenteropancreatic neuroendocrine tumors, with global sales of $816 million in 2025.
Researchers developed a bladder microenvironment-adaptive chemo-immunotherapy system, Gel/UCeNZ/Gem/CpG, to improve local treatment of bladder cancer. The system integrates urease-modified CeO2 nanozymes, gemcitabine, and CpG ODN into an injectable thermosensitive adhesive hydrogel. After intravesical administration it forms a mucosa-adherent depot, prolonging residence and enabling sustained release.
Why it matters: The study demonstrates combined chemotherapy and immune modulation across multiple mechanisms, including amplified oxidative stress and immune microenvironment remodeling, in an orthotopic bladder cancer model.
A liquid biopsy approach detected early-stage pancreatic cancer in a prospective study of 1,785 individuals across four countries. The PANXEON exosome-based biomarker, combined with carbohydrate antigen 19-9 levels, achieved high sensitivity for early-stage pancreatic ductal adenocarcinoma. This offers a blood-based route to earlier detection of a cancer usually found late.
Phase I results for GenFleet's oral KRAS G12D inhibitor GFH375 in advanced solid tumors were published in Nature Medicine. Across 100–900 mg once-daily doses, the drug showed encouraging antitumor activity and manageable safety in heavily pretreated patients with pancreatic cancer and NSCLC.
Ivonescimab, a PD-1/VEGF bispecific antibody, beat Merck's Keytruda on overall survival in the HARMONi-2 study, a phase III head-to-head trial in advanced NSCLC, with median OS of 30.8 months versus 22.6 months and a 27% reduction in relative risk of death. This is the first time a PD-1/VEGF bispecific has defeated Keytruda on overall survival in a phase III head-to-head trial. Akeso and Summit Therapeutics presented the data at the World Conference on Lung Cancer.
Ivonescimab, a PD-1/VEGF bispecific antibody from Akeso, has delivered full overall survival results from the phase 3 HARMONi-2 trial, with a median OS of 30.8 months versus 22.6 months for pembrolizumab monotherapy in a head-to-head comparison. Reported by Caicun Zhou of Shanghai East Hospital, this makes ivonescimab the first cancer immunotherapy to achieve positive results in both progression-free survival and overall survival against pembrolizumab in a randomized, double-blind phase 3 study. A key regulatory decision point arrives in November.
Distinct sets of chromatin regulator (CR) gene mutations predict improved survival after immune checkpoint inhibitor (ICI) treatment in each of ten cancer types, with some CRs recurrently favorable across cancers. Co-occurrence of mutations in two or more CRs further improved survival, and CR-altered tumors consistently showed higher tumor mutational burden than CR-unaltered tumors. Transcriptomic deconvolution linked CR mutations to cancer-type-specific differences in the tumor microenvironment.
