Bai Fan's team published a study in Cancer Cell constructing an epigenetic regulatory map of gastric cancer development and progression. The work reveals a precancerous epigenetically primed state and an acid-driven subtype resistant to immunotherapy.
Why it matters: The study maps epigenetic changes across gastric cancer evolution and links precancerous states to acid-driven immunoresistance, providing a new basis for patient stratification.
Proceedings of the National Academy of Sciences of the United States of AmericaPickScore7676
Matrix stiffness in hepatocellular carcinoma suppresses nanoparticle uptake by driving F-actin polymerization and stress-fiber formation that mechanically damps the plasma membrane-actin interface. Tumor softening with β-aminopropionitrile reduced this mechanical resistance and improved NP penetration and cellular uptake. Combined softening with donafenib-loaded PLGA NPs cut endpoint tumor weight by 87.8% versus free donafenib, but increased pulmonary metastasis, exposing an efficacy-safety trade-off.
Neoadjuvant niraparib monotherapy produced anti-tumour activity and enabled R0 resection in selected patients with HRD-positive, unresectable, high-grade serous ovarian cancer who were initially unsuitable for primary debulking surgery. The authors state the approach remains investigational and requires randomised validation against standard platinum-taxane neoadjuvant chemotherapy.
Why it matters: It suggests a PARP inhibitor could replace platinum-taxane neoadjuvant chemotherapy in HRD-positive ovarian cancer pending randomised testing.
The FDA approved tucatinib (Tukysa, Seagen, a Pfizer subsidiary) with trastuzumab and pertuzumab on October 7, 2026, for maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer after induction therapy. In the 654-patient HER2CLIMB-05 trial, median progression-free survival was 24.9 months with tucatinib 300 mg twice daily versus 16.3 months with placebo (HR 0.64, p<0.0001). The label carries a boxed warning for hepatotoxicity; overall survival data were immature.
Conery et al. report in Nature the discovery and preclinical characterization of TRI-611, a selective, brain-penetrant molecular glue degrader that targets ALK fusion proteins in non-small-cell lung cancer, including tyrosine kinase inhibitor-resistant variants. The approach aims to address acquired resistance driven by ALK kinase domain mutations, TKI toxicity, and limited CNS penetration that hinders treatment of brain metastases. Further preclinical and clinical development would follow.
A Netherlands court blocked sales of Merck's subcutaneous Keytruda Qlex in eight European countries, siding with Halozyme in a patent dispute over its under-the-skin drug delivery technology. Separately, Enliven Therapeutics reached agreement with the FDA on a late-stage trial of relcobitinib in chronic myeloid leukemia, enrolling 450 people to test superiority at spurring a major molecular response. Halozyme is also challenging Merck in a U.S. court after a win in Germany.
A single tRNA species, tRNA1Arg(UCU), is downregulated during prostate cancer lineage plasticity and acts as a key regulator of lineage conversion and therapy resistance. In LNCaP models of the adenocarcinoma-to-lineage-plastic transition, tRNAArg(UCU) was the only significantly downregulated isoacceptor among 49 (DESeq2 log2FC = -0.338, FDR = 2.42 x 10-25). Restoring it sensitizes tumours to AR pathway inhibitors, its dosage controls lineage dependency through translational regulation of SMARCC2, and its loss marks NE prostate cancer and reduced overall survival.
An effector regulatory T cell circuit can be monitored in blood samples to track the development of lung cancer. Blocking this immune network in the preinvasive setting intercepts tumorigenesis, reducing both tumour incidence and size. The work identifies a blood-accessible immune axis that could enable tracking and early intervention before invasive disease.
A Dutch court ruled that Merck infringed a Halozyme Therapeutics patent covering a subcutaneous formulation of Keytruda and ordered the company to stop manufacturing and marketing that version in several European countries, including France, Italy, Sweden, Switzerland and the Netherlands. The decision is part of a widening patent dispute over the cancer treatment. Patients can still access the intravenous version, which is unaffected by the order. Merck was asked for comment.
Caribou Biosciences is discontinuing its two allogeneic CAR-T programmes, vispa-cel for relapsed or refractory B cell non-Hodgkin lymphoma and CB-011 for relapsed or refractory multiple myeloma, and will make substantial workforce cuts, having had 97 full-time employees as of February 2026. CEO Rachel Haurwitz said the financing environment for allogeneic CAR-T made raising capital impossible, as investors shift toward in vivo approaches. The board is now seeking exit routes, including a merger, acquisition, business combination or asset sale.
Why it matters: CRISPR co-founder Jennifer Doudna's Caribou is winding down its pipeline and seeking a buyer, reflecting investor flight to in vivo CAR-T.
A chromatin accessibility atlas of 650 multistage samples from 439 patients traces epigenetic switches across stepwise gastric tumorigenesis, showing that intestinal metaplasia carries a cancer-resembling priming state that licenses tumor initiation. Advanced tumors split into three epigenomic subtypes: proliferative and mesenchymal-inflammatory subtypes respond to neoadjuvant immunotherapy, while the pseudo-gastric subtype is intrinsically drug resistant. FOSL2-driven up-regulation of H+/K+ ATPase transporters sculpts an acidic milieu suppressing CD8+ T cells, and FOSL2 depletion or the acid blocker vonoprazan sensitizes immunotherapy.
Why it matters: It defines an acid-driven immunotherapy-resistant gastric cancer subtype and a clinically available drug, vonoprazan, that reverses it.
FANCM is essential in BRCA1-deficient cells but toxic in BRCA2-deficient cells, where it recruits RMI1/2 to promote replication fork degradation and sensitization to PARP inhibition. An isogenic genome-scale screening platform with acute depletion of BRCA1 or BRCA2 mapped hundreds of genes with shared, distinct, or opposing fitness effects. FANCM loss in BRCA2-deficient cells restored fork integrity and proliferation without restoring homologous recombination, and a FANCM variant disrupting RMI1/2 binding was found in a BRCA2-mutant breast cancer patient with PARP-inhibitor resistance.
Tumors use the transporter SLC52A2 to scavenge vitamin B2 and outcompete T cells, which depend on SLC52A3-mediated B2 uptake. Deprived T cells lose mitochondrial respiration and glutathione regeneration, undergo mitophagy, labile iron accumulation, and lipid peroxidation, and die by ferroptosis. Deleting tumor SLC52A2 restores T cell function in immunocompetent hosts, and B2 supplementation or SLC52A3 overexpression boosts CAR-T antitumor efficacy. High tumoral SLC52A2 correlated with T cell dysfunction and poor survival.
Why it matters: It identifies a specific nutrient-competition mechanism causing T cell ferroptosis and a targetable transporter axis for immunotherapy.
tRNA1Arg(UCU) regulates lineage transitions and therapy resistance in prostate cancer. It reprograms lineage dependence and can be tuned to restore sensitivity to androgen receptor-targeting therapies, operating through a translational program centred on SWI/SNF chromatin remodellers, with TARDBP and ZSCAN29 binding its genomic locus. In patients, tRNA1Arg(UCU) is downregulated in neuroendocrine prostate cancer, and its loss is associated with accelerated metastasis and poor survival.
Serpins help pancreatic ductal adenocarcinoma build a fibrin-rich, immunosuppressive niche, pointing to why PDAC resists anti-PD-1 therapy despite a five-year survival rate of only about 13%. Using the Perturb-map platform, the team combined in vivo CRISPR knockout with Pro-Code protein barcoding and multiplex immunofluorescence imaging, tracking 35 Pro-Code-labeled KPC cells in orthotopic tumors. A Pro-Code/CRISPR library targeting coagulation and fibrinolysis genes, with F8-targeting guide RNA as control, was implanted in the pancreata of immunocompetent mice and spatially imaged at days 7, 14 and 21.
In the CompassHER2-pCR trial, 43.8% of 2,141 early-stage HER2-positive breast cancer patients achieved a pathologic complete response after 12 weeks of neoadjuvant taxane, trastuzumab and pertuzumab, rising to 63.7% in ER-negative disease. The HER2DX test, analyzed in 569 participants, showed pCR rates of 68% with high scores versus 19% with low scores, an association that held after adjustment for clinical factors. The results support using tumor markers to select patients for less intensive chemotherapy.
ArriVent BioPharma announced topline results from the global pivotal Phase III FURVENT trial (NCT05607550). Furmonertinib monotherapy as first-line treatment for advanced non-squamous non-small cell lung cancer with EGFR exon 20 insertion mutations failed to meet the primary endpoint of progression-free survival as assessed by blinded independent central review. The company's share price fell 60% to 63 on the day of the announcement.
Urine cell-free RNA profiling by uRARE-seq, applied to 683 urine samples, detected localized bladder cancer with 95% sensitivity at 90% specificity and outperformed urine tumor DNA analysis. The method detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical BCG. A pretreatment biomarker built from 114 patients predicted BCG versus chemotherapy response with an area under the curve of 0.93 and was strongly associated with recurrence risk.
Estrogen reprograms STING signaling to promote neutrophil extracellular trap formation, creating a functional antigen shield that drives sex-biased resistance to antibody-drug conjugate (ADC) therapy in pancreatic ductal adenocarcinoma (PDAC). The work, from Jihui Hao and Tianxing Zhou's team at Tianjin Medical University Cancer Institute and Hospital, published in Cell, identifies a mechanism linking a basic biological variable, sex, to ADC efficacy, a variable long neglected in ADC clinical trial design.
Firmonertinib missed the primary endpoint of progression-free survival assessed by blinded independent central review in the global phase 3 FURVENT trial as first-line therapy for EGFR exon 20 insertion-mutated non-small cell lung cancer. The three-arm open-label study enrolled 398 untreated patients with locally advanced or metastatic non-squamous NSCLC, comparing once-daily 160mg and 240mg doses against pemetrexed plus platinum chemotherapy. The 240mg arm showed median PFS of 11.0 months versus 9.5 months for chemotherapy, HR 0.75 (95% CI 0.55-1.02), p=0.0654, short of the prespecified significance level.
