Pharmacological degradation of RAF1 via a dTAG-RAF1 mouse model proved efficient and systemically well tolerated but, unlike genetic Raf1 ablation, did not produce tumor regression in KRAS-driven lung adenadenocarcinoma. The N-terminal FKBP12F36V tag perturbed the RAF1 interactome, including scaffold links to apoptotic regulators, blunting the degradation phenotype. Scaffold integrity therefore determines chemogenetic fidelity, and degraders need functional validation, not just target elimination.
Secondary endpoint analyses from the NHS-Galleri randomized controlled trial characterize how a blood-based multi-cancer early detection test performed when added to usual care in more than 142,000 participants without suspicion of cancer. The trial evaluated the test's performance as a screening tool in a general population, offering data on its behavior outside diagnostic settings.
A phase 1b/2 trial tested trastuzumab combined with nivolumab, gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer. The regimen showed encouraging clinical response rates, and HER2 expression was associated with clinical benefit. The results support HER2 status as a marker guiding trastuzumab-based treatment in this population.
Evo2, a genomic foundation model, was used to embed short variants, fusions and rearrangements from 102 patients with soft tissue sarcoma and 129 TCGA-SARC cases into patient-level genomic representations for Cox survival modelling. Adding Evo2 to SARCULATOR raised the OS C-index from 0.620 to 0.770 in the study cohort and from 0.595 to 0.716 in TCGA-SARC; in TCGA-SARC it also improved CINSARC-based OS prediction from 0.476 to 0.653. These descriptive point estimates support altered tumor sequence context as an independent prognostic layer for sarcoma risk stratification.
No results are reported in the available material. The trial randomized patients with localized intermediate-risk prostate cancer to stereotactic body radiotherapy or moderately hypofractionated intensity-modulated radiation therapy. Endpoints were patient-reported urinary irritative/obstructive and bowel quality of life and disease-free survival.
Why it matters: Directly compares two standard radiotherapy options on patient-reported quality of life and survival in localized intermediate-risk prostate cancer.
RP-3467, a selective small-molecule inhibitor of DNA polymerase theta, suppresses Polθ enzymatic activity, abrogates microhomology-mediated end joining, and induces synthetic lethality in homologous recombination-deficient models. Combined with PARP inhibitors olaparib or rucaparib, it produced sustained tumor regression across multiple xenograft and patient-derived xenograft models without added systemic toxicity. In a phase 1 trial (NCT06560632), a heavily pretreated germline BRCA1-mutant ovarian cancer patient with a TP53BP1 loss-of-function mutation achieved a confirmed partial response to RP-3467 plus olaparib by RECIST v1.1.
An iron-dependent pathway drives cancer cachexia-linked events such as adipose browning, work by Chio and colleagues shows. The authors identify methionine sulfoxide reductase A as an important and targetable factor in this process, pointing to a candidate intervention point against cachexia. The finding links iron regulation and methionine redox chemistry to adipose tissue change in cancer.
Iron-activated MSRA is identified as a regulator of PKA in cancer cachexia. MSRA reduces oxidized PKA in white adipose tissue, thereby increasing PKA activity and promoting the wasting syndrome. The finding defines an upstream mechanism controlling PKA activation in adipocytes during cachexia.
A trial compared stereotactic body radiotherapy (SBRT) with moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) in patients with localized intermediate-risk prostate cancer, measuring urinary and bowel quality of life and disease-free survival. The study was designed to test whether SBRT is superior to MH-IMRT on these endpoints. No results are reported here.
Grail's Galleri trial, which randomly assigned 140,000 UK residents to usual care plus multicancer detection testing or usual care alone, failed to meet its primary endpoint of reducing late-stage cancers. Results were presented at the ASCO scientific meeting in June 2026. The outcome sets back the aspirational goal of a single blood test able to identify most cancers.
The FDA approved Eli Lilly's combination drug treatment for patients with an advanced form of breast cancer, reported Sept. 21, 2026. The decision gives Lilly a new option in the advanced breast cancer setting. Full details of the approval are available to STAT+ subscribers.
A blood-based microRNA assay combined with CA19-9, called PANXEON, detected early-stage pancreatic ductal adenocarcinoma in a prospective multicenter study of 1,785 individuals from four countries. The miRNA signature reached an AUC of 88.6% and sensitivity of 83.8% for early-stage PDAC; combined with CA19-9, sensitivity was 86.8% for stage I-II disease, with false-positive rates of 3.2% in low-risk and 15.6% in high-risk controls. It also detected high-grade dysplasia in 64.3% of individuals with high-risk pancreatic cysts.
Telix has agreed to acquire ITM Isotope Technologies Munich for $1.65 billion upfront, gaining an R&D pipeline led by a competitor to Novartis' Lutathera and a radiopharmaceutical supply network. Analysts cited in the coverage are described as extremely bullish on the deal.
Why it matters: The $1.65 billion upfront payment and a pipeline positioned as a direct rival to Novartis' Lutathera are key facts for assessing the deal's industrial reach in radiopharmaceuticals.
First-line fecal microbiota transplantation (FMT) rapidly relieved immune checkpoint inhibitor-related diarrhea and colitis in a cohort from MD Anderson Cancer Center: symptom improvement began at a median of 1.5 days and 76.9% of patients achieved clinical remission. More than eight in ten patients were able to resume their anticancer therapy. The approach positions FMT ahead of high-dose steroids and biologics as initial treatment for this immune toxicity.
Telix Pharmaceuticals will acquire all shares of ITM Isotope Technologies Munich SE in a merger worth at least $1.65 billion, with up to $700 million more payable to ITM shareholders if ITM's lead drug meets regulatory and sales goals. The deal combines two radiopharmaceutical companies and creates a well-resourced player in a field dominated by Novartis, which launched two radioactive isotope cancer treatments in 2018 and 2022.
Ataraxis Breast CTX, a causal multi-modal AI model combining clinical variables with H&E histopathology, stratified residual recurrence risk in 556 node-positive HR+/HER2- breast cancer patients from the UNIRAD trial. Five-year disease-free survival was 93% in the low-risk group versus 80% in the high-risk group, and CTX-benefit predicted everolimus benefit in an exploratory multivariable analysis (interaction p = 0.01). The model may inform selection of patients for adjuvant treatment escalation.
BMI at diagnosis shows a U-shaped association with recurrence-free survival in early-onset colorectal cancer, with the lowest hazard at BMI 27 and the highest at BMI below 20 or above 30 (LRT p=0.02). In 1,459 curative-intent surgery patients, no such association appeared in average-onset colorectal cancer (LRT p=0.15), and the cohorts differed significantly (LRT p=0.046). The findings suggest the obesity paradox may be specific to EOCRC.
Knowledge-guided tumor microenvironment gene-set features outperform data-driven transcriptome-wide gene selection for predicting atezolizumab response in advanced urothelial carcinoma. In 298 IMvigor210 patients, they improved AUPRC by 0.058 over clinical variables, but gains shrank to +0.011 beyond TMB and PD-L1, and data-driven selection was unstable (Jaccard 0.227) with AUPRC 0.150 lower. The pattern replicated in an external cohort (+0.128 vs +0.019).
Melanomas harbor decidual-like NK cells with a CD56 Bright CD16 - CD49a + CD9 + phenotype, a population rare or absent in peripheral blood from patients with melanoma and healthy donors. The cells appear in tumors across sex, melanoma subtype, and disease site, and tumor CD9 expression correlated with intratumoral dl-NK frequency (Pearson rho = 0.40, p = 0.056). Co-culture showed direct contact with CD9-expressing melanoma cells induces CD9 acquisition by NK cells, suggesting an immunologic parallel between melanoma and the maternal-fetal interface.
In a French nationwide cohort of 95,015 adults initiating immune checkpoint inhibitor therapy, mRNA COVID-19 vaccination within 100 days before or after ICI start was associated with modestly lower early all-cause mortality (pre-ICI HR 0.90 at 1-3 months; post-ICI HR 0.84 at 3 months), with no significant association after 12 months. Similar patterns for non-mRNA COVID-19 and other adult vaccines point to healthy-vaccinee effects rather than a specific mRNA vaccine benefit.
Why it matters: Population-scale evidence that the observed survival signal after COVID-19 vaccination near ICI start is likely a healthy-vaccinee effect.
