Myeloid reprogramming generates myeloid-derived activating cells to potentiate radiotherapy and suppress metastasis

Ji et al. show that radiotherapy induces a TET2-dependent epitranscriptomic program in myeloid cells that promotes immunosuppressive M-MDSC differentiation. TET2 loss preserves caRNA m5C-MBD6 signaling, restores IRF3-IFN-I activation, generates myeloid-derived activating cells, and enhances radiotherapy-induced antitumor immunity.

dlvr.it

Beyond genes and hotspots: Protein-informed interpretation of cancer mutations

Interpreting the biological and clinical significance of somatic mutations in cancer genomes remains challenging. In this issue of Cancer Cell, Hyeon et al. identify and map significantly mutated regions to protein domains and structural features, establishing a proteo-genomics framework for interpreting cancer mutations beyond genes and hotspots.

dlvr.it

Chemotherapy-free phase 1/2 trial of HRS-4642 plus adebrelimab in previously treated metastatic KRAS G12D-mutant pancreatic cancer

Shi et al. report the first clinical study of the selective KRAS G12D inhibitor HRS-4642 combined with the anti-PD-L1 antibody adebrelimab in heavily pretreated patients with KRAS G12D-mutant pancreatic cancer. The chemotherapy-free regimen demonstrates a manageable safety profile and preliminary antitumor activity, supporting its feasibility as a targeted strategy in this molecularly defined subset.

dlvr.it

Chronotherapy with immune checkpoint inhibitors: The knowns, the unknowns, and the contested

Emerging data indicate that immune checkpoint inhibitors can exhibit time-of-day-dependent effects in pre-clinical models. Furthermore, multiple retrospective clinical trials associate earlier anti-tumor treatment timing with improved outcomes. However, key questions remain regarding the reproducibility of these findings, the underlying mechanisms, and their clinical implications. This commentary discusses these open questions and provides an outlook on the field.

dlvr.it

Molecular residual disease: Charting a new path for treating resectable solid tumors

Molecular residual disease (MRD), detected via circulating tumor DNA (ctDNA) after curative-intent surgery, identifies resectable solid tumor patients at high recurrence risk, thereby enabling enriched trials with larger effect sizes and smaller samples. Yet enrichment narrows the eligible population and thus challenges conventional randomized designs. We propose an MRD Registry as an external control cohort that integrates quantitative ctDNA data with outcomes to validate ctDNA dynamics as response indicators—facilitating efficient MRD-based trial design and accelerating novel therapy development.

dlvr.it

Pancreatic ductal adenocarcinoma: The Vision of Heracles

Pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, as tumors evolve faster than therapies. Resistance is ecological, not merely KRAS driven, involving overlooked players like high-grade pancreatic intraepithelial neoplasias (PanINs), peripancreatic fat, stromal mechanics, myeloid-neural circuits, metabolic rewiring, and systemic host responses. We propose precision interception targeting PanIN/intraductal papillary mucinous neoplasm (IPMN) biology, spatial-functional-proteogenomic classification beyond transcriptomics, the Heracles Protocol (measure, prime, strike, and adapt), and integrated technologies from AI pathology to exosomal delivery and CRISPR-based synergy mapping, together making PDAC more tractable.

dlvr.it

Scherer’s map, remapped

Scherer’s century-old classification of expansive and infiltrative glioma growth remains foundational to neuro-oncology. In this issue of Cancer Cell, Hoefflin et al. use spatial RNA and protein profiling of IDH-mutant gliomas to reveal hypoxia and necrosis as organizing centers of expansive growth and white-matter tracts as guides and constraints on invasion.

dlvr.it

Spatial analysis reveals the evolving organization of IDH-mutant glioma

Hoefflin et al. define organizational principles of IDH-mutant gliomas using multimodal spatial profiling. They identify three spatial archetypes across histological grades and reveal that brain anatomy and hypoxia represent distinct spatial organizing forces, with the white-gray matter junction acting as a functional barrier to invasion.

dlvr.it

TIME in motion: How response takes shape

Biomarkers for immune checkpoint inhibitors have largely treated the tumor immune microenvironment as a fixed property. In this issue of Cancer Cell, Lin et al. assemble a longitudinal pan-cancer single-cell atlas and show that the direction of immune-state remodeling during therapy is more informative than baseline composition.

dlvr.it

Tumor evolution shapes metastatic competence in colorectal cancer

In this issue of Cancer Cell, Manca et al. investigate the genomic evolution and metastatic tropism of over 7,000 colorectal cancers. Integrating primary tumor location, genomic alterations, and clinical variables, they reveal how distinct patterns of tumor evolution shape metastatic competence and impact organ tropism, offering a framework to refine surveillance.

dlvr.it

Integrated clinicogenomic analysis reveals the evolution and metastatic tropisms of advanced colorectal cancer

Manca et al. analyze >7,000 colorectal cancers, integrating next-generation sequencing and clinical data. They define tumor genomics, clonality and dosage of mutations, and metastatic tropisms and their effects on patient outcomes. Incorporating metastatic sites, primary tumor location, and genomics, they develop an organ-specific risk model for metastasis.

dlvr.it

Tumor immune microenvironment remodeling predicts response to checkpoint inhibitor therapy

Lin et al. assemble a longitudinal pan-cancer single-cell atlas that tracks how the tumor immune microenvironment remodels during checkpoint inhibitor therapy. They show that the direction of remodeling, rather than the pre-treatment state, predicts response and translate these dynamics into a baseline gene signature that forecasts outcome across cancer types.

dlvr.it

Axes of biological variation in diffuse large B cell lymphoma

(Cancer Cell 44, 567–585.e1–e12; March 9, 2026)

dlvr.it

MDMX acts as a pervasive preleukemic-to-acute myeloid leukemia transition mechanism

(Cancer Cell 39, 529–547.e1–e7; April 12, 2021)

dlvr.it

Biological aging and the hidden architecture of early-onset cancer risk

Across birth cohorts, in a Nature Medicine study, Tian et al. identify larger biological age gaps associated with early-onset lung, colorectal, and uterine cancers across birth cohorts. These findings position biological age as an integrative marker of physiological dysregulation. Future work combining aging clocks and mutational signatures could distinguish tumor-promoting states from tumor-initiating exposures.

dlvr.it

Tumor-infiltrating plasma cell targets as a source for immunotherapies

Tumor-infiltrating plasma cells are key responders to immunotherapy. In this issue of Cancer Cell, Meyerhoff et al. show that plasma cells from lung lesions of anti-PD-1-treated patients target citrullinated proteins. Engineering CAR T cells with these plasma cells scFv reveals anti-tumor specificity without adverse effects, identifying therapeutic opportunities.

dlvr.it

Tumor-infiltrating plasma cell profiling after PD-1 blockade reveals tumor-specific antibodies

Meyerhoff et al. identify tumor-infiltrating plasma cells as a source of antibodies with therapeutic potential. Their lead antibody, PC-1, recognizes citrullinated antigens on cancer and tumor-promoting myeloid cells and can be repurposed to guide CAR T cell therapy.

dlvr.it

A self-amplifying nerve-fibroblast circuit drives colorectal cancer progression

Kobayashi et al. demonstrate that cholinergic signaling induces NTN1 secretion from colorectal CAFs, which in turn enhances intratumoral cholinergic innervation. Increased acetylcholine and CAF-derived NTN1 then accelerate cancer cell growth through tumoral CHRM3 and UNC5B. Blocking CHRM3 or NTN1 may represent a promising therapeutic approach for CRC.

dlvr.it

EGFR-targeting ADCs: From oncogene addiction to antigen-guided drug delivery

In this issue of Cancer Cell, Li et al. report a first-in-human phase 1 study of SYS6010, an epidermal growth factor receptor (EGFR)-targeting antibody-drug conjugate, in advanced solid tumors. The study highlights how EGFR-directed therapy moves beyond kinase inhibition toward antigen-guided cytotoxic delivery in non-small cell lung cancer.

dlvr.it

SYS6010, epidermal growth factor receptor-targeting antibody-drug conjugate for advanced non-small cell lung cancer: A phase 1 trial

Li et al. report results from a first-in-human study showing that SYS6010, an EGFR-targeted antibody-drug conjugate, demonstrates encouraging antitumor activity with a tolerable safety profile in pretreated advanced NSCLC, providing evidence that warrants further clinical development.

dlvr.it

Retraction Notice to: Methionine restriction promotes cGAS activation and chromatin untethering through demethylation to enhance antitumor immunity

(Cancer Cell 41, 1118–1133.e1–e12; June 12, 2023)

dlvr.it

Latent tumor killers awakened

In this issue of Cancer Cell, Kehl et al. construct a single-cell atlas of bone marrow T cells from patients with bone marrow-resident malignancies, identifying tumor-reactive populations existing in a state of latent competence. A 15-gene signature identifies this subset, which is expanded by immunotherapies and predicts clinical responses.

dlvr.it

Latent effector T cells mediate immunotherapy responses in the bone marrow microenvironment

Kehl et al. characterize tumor-reactive T cells in the bone marrow of patients with multiple myeloma and AML. These cells adopt an effector state distinct from exhausted solid tumor TILs. The TFiT classifier stratifies immunotherapy, but not chemotherapy, response, identifying a latent, therapeutically engageable anti-tumor compartment.

dlvr.it

A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer

Zheng et al. identify a PIKfyve-ER stress-lipogenesis axis that enables neuroendocrine prostate cancer cells to tolerate elevated basal ER stress through PIKfyve-dependent lysosomal homeostasis and SREBP-driven lipogenesis. Dual inhibition of PIKfyve and FASN disrupts these adaptive pathways, driving terminal UPR activation and apoptosis and providing a robust translational strategy.

dlvr.it

Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction

Li et al. identify a previously unrecognized NK cell subset that limits cord blood-derived CAR-NK cell therapy by diverting tumor targeting and promoting self-directed fratricide and show that donor cell composition shapes efficacy while offering a practical manufacturing strategy to improve consistency, persistence, and antitumor activity of off-the-shelf CAR-NK therapies.

dlvr.it

Teamwork makes the dream work? Ensemble learning in computational pathology

In this issue of Cancer Cell, Luo et al. report an ensemble approach that integrates five pretrained pathology foundation models into a slide-level representation to exploit their complementary information, yielding improvements in tumor subtyping, biomarker, and therapy-response prediction. This shows the potential of ensemble and multimodal approaches in computational pathology.

dlvr.it

Ensemble learning of pathology foundation models for precision oncology

Luo et al. develop ELF, a framework that ensembles five pathology foundation models to generate unified representations from whole-slide images. Trained on nearly 54,000 slides across 20 anatomical sites, ELF outperforms individual foundation models in disease classification, biomarker detection, and prediction of response to chemotherapy, targeted therapy, and immunotherapy.

dlvr.it

UniCure: A multi-modal model for predicting personalized cancer therapy response

Chen et al. present UniCure, a multi-modal foundation model that predicts drug-induced transcriptomic responses across diverse cellular contexts. By bridging cancer cell line data with patient-derived models, UniCure enables personalized drug prioritization and patient stratification, with its predicted therapeutic rankings correlating strongly with clinical survival outcomes in real-world cohorts.

dlvr.it

Retraction Notice to: Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity

(Cancer Cell 41, 1170–1185.e1–e12; June 12, 2023)

dlvr.it