Common Fc function-silencing mutations in therapeutic IgG1 fail to eliminate FCRL5 binding, so Fc effector function is attenuated rather than silenced. The FCRL5-IgG1 Fc crystal structure, solved at 3.4 Å, shows a 1:1 complex with a binding mode distinct from classical Fcγ receptors. Fc-engineered antibodies selectively engaging FCRL5 inhibited B cell receptor-induced Ca2+ flux in FCRL5-expressing B cells, revealing a pathway for B cell modulation relevant to multiple myeloma targeting.
Dizhe Pharmaceutical (Dizhe Medicine) said its July 14, 2026 license agreement with AstraZeneca has taken effect, granting AstraZeneca exclusive worldwide rights to develop and commercialize Sunvozertinib (Shuwozhe). AstraZeneca plans to launch the drug in the US in the fourth quarter of this year. Dizhe receives a $600 million upfront payment, up to $400 million in clinical development milestones, up to $500 million in sales milestones, and tiered royalties on global sales from high single to low double digits.
Dizhe Pharmaceutical (Dizhe Pharmaceutical) has filed an H-share listing application with the Hong Kong Stock Exchange in August 2026, four years after raising about 2.1 billion yuan on the STAR Market. Concurrently, a global exclusive license with AstraZeneca for sunvozertinib (sunvozertinib, DZD9008), effective August 31, gives Dizhe a $600 million upfront payment, up to $400 million in development milestones and up to $500 million in sales milestones, plus tiered royalties; AstraZeneca will commercialize the EGFR exon20ins NSCLC drug in the US in Q4 2026. Dizhe posted 522 million yuan in revenue in H1 2026 and will channel proceeds into clinical development of golidocitinib, DZD6008 and birutinib (DZD8586).
Genome-wide screens across eight Myotis species, plus structural-variation analyses and experiments in primary cells, show bats adapt differently to DNA and RNA viruses than other mammals: positive selection is over-represented for DNA-virus-interacting proteins, while RNA-virus-interacting proteins show elevated copy-number variation. Myotis-specific EIF2AK2 (PKR) duplications carry ancient trans-species copy-number polymorphisms, and recurrent longevity is linked to selection in cancer pathways and a unique DNA damage response in Myotis lucifugus cells.
Why it matters: It links bat longevity and viral tolerance to specific genomic mechanisms, including selection in cancer pathways and EIF2AK2 duplications.
Adding atezolizumab to neoadjuvant chemotherapy did not improve event-free survival in the phase 3 NSABP B-59/GeparDouze trial of patients with early-stage triple-negative breast cancer, missing its primary endpoint. Translational analyses identified tumor microenvironment-dependent determinants of response, indicating basal-like immune-activated tumors may respond to atezolizumab plus chemotherapy.
Why it matters: Negative phase 3 result for atezolizumab in early triple-negative breast cancer, with biomarker data indicating which tumors may still benefit.
KRAS-mutant intrahepatic cholangiocarcinoma carries the worst prognosis among metabolic subtypes, marked by enriched COX/arachidonic acid metabolism. KRAS mutation activates NF-κB to upregulate CXCL5, recruiting CXCR2+ PMN-MDSCs, while tumor-derived PGE2 boosts AA uptake and COX-2 in those cells, forming a feedback loop that suppresses CD8+ T cells via EP4. Targeting the COX-2-PGE2-EP4 axis combined with anti-PD-1 showed synergistic efficacy in KRAS-mutant mouse models and patient-derived tumor fragments.
In resected colorectal liver metastases, the presence of circulating tumor DNA-defined molecular residual disease was evaluated for its association with survival outcomes and for whether it identifies patients who derive differential benefit from adjuvant chemotherapy. The analysis addresses ctDNA status as a potential guide to adjuvant treatment decisions after metastasectomy.
Why it matters: It tests whether ctDNA-defined molecular residual disease can guide adjuvant chemotherapy decisions after colorectal liver metastasis resection.
Mitochondrial complex I deficiency, driven by loss of the subunit NDUFA9, undermines natural killer (NK) cell function in glioblastoma. NDUFA9 abundance in NK cells informed patient outcomes, and Ndufa9 knockout shifted NK cells toward glutamine dependence and repressive H3K27me3 epigenetic marking. Resveratrol-mediated NDUFA9 activation or its overexpression restored complex I activity and enhanced NK cell anti-GBM function, marking complex I as a pharmacologically targetable node for NK cell-based immunotherapy.
Lightsheet microscopy on intact tumors pinpointed junctions between precancerous and invasive regions, and a multimodal serial-section workflow combining volumetric reconstruction with spatial transcriptomics analyzed 319 spatial assays from 51 cases. In breast cancer, loss of MGP and PLAT marked and promoted invasive transition; in prostate cancer, GDF15, ALDH1A3, ANPEP and FASN rose with invasion and their knockdown suppressed PC-3 proliferation and migration. The approach exposes spatially defined drivers of invasion and candidate targets in the two most prevalent cancers.
Rare disseminated tumor cells enter a transient PHGDH-high state that allows them to evade immunity and drive metastatic outgrowth. The work frames a progression from immune clearance to dormancy to outgrowth, with the cells coevolving with their microenvironment. Targeting PHGDH or CX3CR1-high macrophages may stop dormant tumor cells from progressing to metastases.
TNG961, an oral molecular glue degrader of HBS1L, exploits the synthetic lethal dependency that FOCAD deletion creates on the HBS1L-PELO ribosome rescue complex. FOCAD is deleted in about 1 in 3 MTAP-deleted cancers. TNG961 disrupts the HBS1L-PELO complex, causing translational arrest, and oral dosing regressed FOCAD-negative xenografts, including PRMT5 inhibitor-refractory models.
Why it matters: It defines HBS1L degradation as a precision strategy for common chr9p21 co-deletion cancers, including PRMT5 inhibitor-refractory tumors.
IL1RAP, a surface protein induced by oncofusions such as EWSR1-ETS in Ewing sarcoma, NPM-ALK in anaplastic large cell lymphoma, and ETV6-NTRK3 in multiple tumor types, can be targeted with engineered antibody-drug conjugates. The ADCs induced durable regression of Ewing sarcoma xenografts, reduced metastatic dissemination, and blocked growth of ALCL xenografts and syngeneic ETV6-NTRK3+ sarcomas in vivo. No detectable normal tissue toxicity, including in nonhuman primates, supports clinical translation.
Longitudinal whole-genome and targeted sequencing in 30 patients with Philadelphia-negative myeloproliferative neoplasms, integrated with 7,986 blood counts, shows that progression to leukemia is genomically encoded years before clinical transformation. Leukemic transformation arose via TP53 loss, stepwise driver acquisition in complex clones, or independent leukemic clones, while stable disease maintained long-term clonal equilibrium without new drivers. Sequencing of 203 colony genomes indicated non-neoplastic origins for some triple-negative essential thrombocythemia, and therapy-associated mutagenesis followed azacitidine and hydroxycarbamide exposure. The work supports serial genomic monitoring for risk stratification.
Why it matters: It shows myeloproliferative neoplasm progression is genomically detectable years before clinical transformation, supporting serial monitoring.
China has approved satricabtagene autoleucel (satri-cel), the first CAR T-cell therapy for solid tumors, for patients with claudin 18.2-positive, HER2-negative gastric or gastro-esophageal junction cancer. The approval is based on a phase II trial showing improved progression-free and overall survival. Scientists welcome the decision but say more research is needed to improve CAR T-cell effectiveness against solid tumors.
Spatial proteomics of biopsies from the SWOG S1616 trial shows that melanoma patients responding to ipilimumab plus nivolumab after primary resistance to anti-PD-1 have activated CD8 T-cell networks near melanoma cells, while progressing biopsies show impaired T-cell infiltration adjacent to plasma cells. Responding baseline biopsies also showed complement expression in myeloid cells, interferon pathways in endothelial cells, and oxidative phosphorylation and lipid metabolism in melanoma cells. The work defines tumor microenvironment features that accompany reversal of anti-PD-1 resistance.
ORION-FISH combines high-plex tissue imaging with morphology-preserving DNA-FISH and single-cell registration to measure copy-number alterations alongside protein-defined cell states in intact tissue, with results concordant with clinical FISH. In high-grade serous ovarian carcinoma it recapitulated known chromosomal changes and revealed subclonal heterogeneity missed by targeted sequencing. In serous tubal intraepithelial carcinomas it found intermixed cells with MYC or CCNE1 gains linked to distinct immune microenvironments, and detected MYC and CCNE1 gains in morphologically normal fallopian tube epithelium, plus rare MDM4 increases.
A recyclable lysosome-targeting chimera built from a polyzwitterion and a protein-of-interest ligand triggers macropinocytosis and degrades membrane or extracellular proteins without a dedicated receptor. The chimera dissociates in acidic endosomes, exits the cell via the endoplasmic reticulum-Golgi transcytosis pathway, and re-enters further degradation cycles. In a triple-negative breast cancer mouse model, these McR-TACs durably degraded programmed cell death ligand 1 or macrophage migration inhibitory factor and inhibited tumor growth.
The FDA approved Revolution Medicines' RASONQUE (daraxonrasib) on August 26 for metastatic pancreatic cancer. It is the first approved drug worldwide to directly target RAS. The approval marks a first for the RAS-targeting class in pancreatic cancer.
Belzutifan plus lenvatinib extended progression-free survival over cabozantinib in previously treated advanced clear-cell renal cell carcinoma. In the phase 3 LITESPARK-011 trial, 747 patients with disease progression after anti-PD-1 or anti-PD-L1 therapy were randomly assigned to belzutifan-lenvatinib or cabozantinib. Progression-free survival by masked independent central review was significantly longer with belzutifan-lenvatinib, while overall survival did not differ significantly, and the authors suggest belzutifan-lenvatinib may become a new standard of care in this setting.
A binding-to-release strategy decouples payload release from receptor endocytosis by placing an electrophile cleaved by a nucleophilic residue in the target binding pocket, implemented through phosphorus(V)-phenol exchange chemistry. A FAP-targeted SMDC built this way achieved 5.9-fold higher tumour MMAE exposure (AUC0-120 h) than an internalization-dependent FAP-SMDC, tumour-to-blood ratios 14.7- and 3.6-fold higher than FAP-ITR-SMDC and FAP-ITR-ADC, tumour-to-liver ratios 55.1- and 58.7-fold higher, and near-complete tumour regression across tumour models. The approach also extended to PD-L1 and an mRNA-display-derived FAP peptide, broadening the target scope for conjugates.
