Systematic mapping of splicing within and between transposable elements across cancers defines TEtrans, a tumor-enriched class of gene-independent transcripts. TEtrans show distinct regulatory programs and can act as oncogenic RNAs or encode immunogenic tumor antigens, expanding the known functional landscape of TE reactivation in cancer.
PHYHD1 acts as a tumor suppressor in renal cell carcinoma by restraining protein translation. Progressive PHYHD1 loss predicts poor prognosis, while restoring it suppresses tumor growth in RCC cell and patient-derived xenograft models independently of its dioxygenase activity. Mechanistically, PHYHD1 binds eEF1A1, alters its ribosome association, and limits translation of ceramide transporter CERT1, whose targeting impairs proliferation of PHYHD1-deficient cells.
Adding intravenous VCN-01, a hyaluronidase-expressing oncolytic adenovirus, to gemcitabine and nab-paclitaxel improved outcomes as first-line therapy in metastatic pancreatic ductal adenocarcinoma. In the full analysis set, median overall survival was 10.8 versus 8.6 months (HR 0.57) and progression-free survival was 7.0 versus 4.6 months (HR 0.55, P = 0.011); response duration was 11.2 versus 5.4 months. The phase 3 evaluation is warranted.
Ligand-directed lipid nanoparticles were used to engineer chimeric antigen receptor natural killer cells directly in vivo, an approach that avoids the ex vivo manufacturing central to current CAR cell therapies. The method targets NK cells with mRNA lipid nanoparticles carrying a ligand-directed delivery design. It moves CAR-NK immunotherapy toward a ready-to-administer, in-house production model.
Bristol Myers Squibb's radiopharmaceutical RYZ101 (225Ac-DOTATATE) met the primary endpoint of progression-free survival in the phase 3 ACTION-1 trial. Blinded independent central review showed a statistically significant and clinically meaningful improvement over investigator's choice of standard therapy, with safety consistent with the previously known profile.
Why it matters: The phase 3 ACTION-1 trial met its PFS endpoint in SSTR+ GEP-NETs patients who progressed after prior Lu-177 therapy, enabling comparison with existing treatments in this line.
On September 29, 2026, the NMPA approved the breast cancer indication for paclitaxel oral solution (brand name Bairuisu), a product of 3SBio and Shanghai Haihe Pharmaceutical, for recurrent or metastatic HER2-negative breast cancer. The drug, the first oral paclitaxel formulation worldwide, was previously approved in September 2024 as second-line treatment for advanced gastric cancer. Its use now extends from gastric to breast cancer, offering an oral option for a chemotherapy long given only by injection.
Adding epcoritamab to R-CHOP cut the risk of disease progression or death by 51% in previously untreated DLBCL patients with IPI scores of 3 to 5 (HR 0.49; 95% CI, 0.35-0.69; P<0.0001), meeting the primary endpoint of the phase 3 EPCORE DLBCL-2 trial. The benefit was matched in the overall IPI 2 to 5 population (HR 0.49; 95% CI, 0.36-0.67; P<0.0001). This is the first positive phase 3 study of a bispecific antibody combination in first-line DLBCL.
In 52,236 patients with cancer, cachectic weight loss episodes coincided with disease progression, were linked to lower survival rates, and shared a consistent serological signature across routine laboratory markers. TP53 mutations and other specific tumor genotypes were positively associated with cachexia risk, and statistical models were trained to predict impending cachexia risk.
China's NMPA has approved the marketing application for Foresee Pharmaceuticals' Camcevi 42 mg for advanced prostate cancer in adults. The drug is a ready-to-use, six-month subcutaneous depot formulation of leuprolide mesylate. GenSci holds exclusive commercialization rights in China, covering central precocious puberty, premenopausal breast cancer, and advanced prostate cancer.
The histone H2B mutation H2BE113K acts as an oncohistone that promotes breast cancer spread without affecting tumor growth. In CRISPR-Cas9 knock-in cells and gene-edited mice, the mutation boosted colony formation and lung metastasis but not proliferation or migration, working through recruitment of the chromatin remodeling protein SMARCA5 to upregulate G3BP2. The SMARCA5 inhibitor ED2-AD101 curbed the excess colony formation in mutant cells.
Organoid-based drug testing plus genomic characterization was feasible but limited by PDO establishment in HER2-negative metastatic breast cancer. Of 15 patients enrolled, 10 biopsies had adequate tumor content and PDOs were established in 4, an overall success rate of 40%, missing the primary endpoint of at least 46%. Results returned within 12 weeks informed treatment selection in all evaluable cases, and physicians used the information in 100% of successful cases.
Why it matters: Quantifies the real-world success rate of functional precision oncology in metastatic breast cancer, showing PDO establishment as the bottleneck.
Patient-keyed pooling of cBioPortal studies lets blood-normal specimens from clonal-hematopoiesis studies contaminate tumor mutation matrices, because shared patient identifiers merge hematopoietic clones into solid-tumor calls. Across 1,282,483 coding calls from 483 studies, 52.8% of patients flagged DNMT3A-mutant carry no tumor-derived call, versus 0.4% for TP53, and correction lowers the pan-cancer DNMT3A rate by 45%. Two pre-aggregation filter lines remove the contamination, which reaches 65 other cohorts.
Standard bulk partial EMT (pEMT) scores in head and neck squamous cell carcinoma mainly measure stroma: across three single-cell datasets, the malignant arm (laminin-332 and hemidesmosome genes) sat in malignant cells while the stromal arm (fibrillar collagens, vimentin) sat in fibroblasts. A classifier and 12-gene core recovering the malignant arm predicted long progression-free survival in 40 patients given platinum and cetuximab (AUC 0.78 and 0.82), but the malignant arm tracked the Basal subtype, whose score performed as well or better (0.93) and also in two xenograft panels.
Trastuzumab deruxtecan (T-DXd) inhibited all subcutaneous melanoma PDXs and outperformed trastuzumab emtansine (T-DM1), which had limited activity, while liver models were less sensitive. Parental and ERBB2-knockout xenografts responded similarly at first, though knockout tumors regrew earlier, and melanoma cells resisted both ADCs in vitro with little trastuzumab uptake. Tumor-derived cathepsin L found outside melanoma cells suggests payload release can occur extracellularly, independent of HER2.
The FDA in August approved Revolution Medicines' RAS inhibitor Rasonque (daraxonrasib) for metastatic pancreatic ductal adenocarcinoma. It is the first drug in the RAS class for this indication.
Why it matters: The article compares the first pan-RAS inhibitor Rasonque mechanistically with existing KRAS G12C inhibitors, helping readers place it in RAS-pathway therapy.
PHYHD1 acts as a tumor suppressor in renal cell carcinoma by controlling protein production. Its loss drives disease progression through increased production of ceramide transporter 1 (CERT1). The PHYHD1-CERT1 regulatory pathway may help predict patient outcomes and offers a therapeutic opportunity for PHYHD1-deficient tumors.
Bristol Myers Squibb's RYZ101, an actinium-225-based radiopharmaceutical acquired in the $4.1 billion RayzeBio deal, met the primary endpoint in an interim analysis of the Phase 3 ACTION-1 study, showing a statistically significant and clinically meaningful improvement in progression-free survival by blinded independent central review. The trial enrolled patients with advanced somatostatin receptor-expressing GEP-NETs that progressed after Lutathera, and these are the first Phase 3 results for an alpha-isotope targeted radiopharmaceutical therapy in any indication.
Why it matters: First Phase 3 readout for an actinium-225 alpha-isotope radiopharmaceutical, a potential new option after Lutathera progression in GEP-NETs.
FDA review documents show that Revolution Medicines' RAS inhibitor Rasonque, approved early for pancreatic adenocarcinoma, performed unevenly across KRAS mutation subtypes in the Phase 3 RASolute 302 trial. Overall ORR was 33%, but patients with G12V mutations reached 50%, G12D patients 24%, and the small G12R cohort just 7%, below the chemotherapy control. Analysts at Leerink and Truist called the gap exploratory and still expect a record launch, with Truist projecting $2.3 billion in sales by 2028 if the drug moves into first-line disease.
Single-micronucleus sequencing and live-cell imaging of cancer cells, together with analyses of neuroblastoma biopsies, show that extrachromosomal DNA (ecDNA) residing in micronuclei constrains tumor cell fitness. In patients with neuroblastoma, micronuclear ecDNA was associated with favorable survival. The work identifies micronuclear localization of ecDNA as a feature linked to reduced tumor fitness rather than unchecked growth.
A multimodal atlas of cancer cachexia built from longitudinal data on 52,236 patients with cancer shows that weight loss episodes are linked to systemic serologic signatures and specific tumor genotypes. Integrated clinical and molecular data predicted these episodes, enabling earlier identification of cachexia.
