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Preprints

New results on bioRxiv and medRxiv, before peer review.

100 selectedRelated topicsOriginal researchMethods and resourcesSingle-cell and spatial omics

Latest picks

41–60 of 100
Oct 1Thu
  1. medRxiv Oncology46

    Axitinib in Progressive Metastatic Pheochromocytoma and Paraganglioma: Results of a Phase II Study

    Single-agent axitinib produced confirmed partial responses in 35.3% of 17 treated patients with progressive metastatic or unresectable pheochromocytoma and paraganglioma, with median progression-free survival of 7.9 months and median overall survival of 29 months. Hypertension occurred in 79% of patients but was managed with antihypertensive therapy and dose modification, and no patient stopped treatment for toxicity. The phase II trial's efficacy compares favorably with sunitinib in this rare disease.

    Why it matters: First prospective single-arm data on selective VEGFR inhibition with axitinib in a rare cancer with few systemic options.

Sep 30Wed
  1. bioRxiv Cancer Biology70

    RNA splicing factor mutations drive myeloid neoplasm oncogenesis through protein complex poisoning

    Splicing factor mutations in myeloid neoplasms poison entire functional protein complexes, not just individual transcripts. Single-cell transcriptomics (10X-ONT, n = 21) and immunophenotype-resolved pauciproteomics (n = 78) across 62 patients and 20 healthy donors show that mutation-specific RNA mis-splicing decouples protein from transcript dynamics during hematopoietic differentiation, effects invisible to transcriptomics alone and validated in iPSC differentiation models.

    Why it matters: Protein-level consequences of splicing factor mutations are invisible to transcriptomics, changing how these oncogenic events should be studied.

  2. medRxiv Oncology72

    CD3-engaging bispecific antibodies convert human regulatory T cells into cytotoxic effectors

    CD3-engaging bispecific T cell engagers convert human FOXP3+ regulatory T cells into an AP-1-imprinted hybrid cytotoxic state that contributes to tumor clearance. In newly diagnosed multiple myeloma patients treated with BTCE-based induction in the phase 2 GMMG-HD10/DSMM-XX/MajesTEC-5 trial, single-cell sequencing showed Tregs expressing GZMA, GNLY and NKG7, and in vitro BTCE-exposed Tregs killed tumor cells in a target- and dose-dependent manner. IMiDs amplified and reshaped this cytotoxic program, supporting BTCE-IMiD combination regimens.

    Why it matters: Reframes Tregs as active cytotoxic effectors of bispecific antibody therapy and gives a mechanistic basis for BTCE-IMiD combinations.

  3. bioRxiv Genomics57

    Disease relevance and replicability of deep learning gene expression prediction

    Deep learning models that predict gene expression from DNA sequence owe their high overall correlation mostly to capturing whether genes are on or off, not to disease-relevant changes in expression among active genes; performance rises with how bimodal a gene's expression distribution is. The authors also found inconsistencies between published code and reported performance, and conclude that personalized genomic prediction in disease remains far from solved.

    Why it matters: Reported performance of popular gene-expression prediction models overstates their usefulness for disease research.

  4. bioRxiv Cancer Biology38

    Circadian gene-network distortion in high-risk neuroblastoma across multiple biological reference contexts

    High-risk neuroblastoma shows robust disruption of coordinated circadian gene network organisation, and the alteration is distributed across the network rather than driven by single clock genes. Delta-CCD, a measure of network dysregulation, was highest in high-risk tumours in two cohorts (SEQC, n=498; Kocak, n=649) across canonical, adrenal-tissue matched and developmental references. MYCN-amplified and stage 4 tumours showed a more reference-dependent pattern, strongest in the adrenal context.

    Why it matters: It reframes circadian disruption in high-risk neuroblastoma as a network-level alteration, not a single-gene effect, across two cohorts.

  5. bioRxiv Cancer Biology66

    Tissue resident CD4+ memory T-cells mark response to immune checkpoint inhibition in high-grade glioma

    Tissue-resident CD4+ memory T cells mark which high-grade gliomas respond to combined PD-1 and CTLA-4 inhibition. In a syngeneic hypermutated glioma model, response involved clonal expansion of tumor-reactive cytotoxic T cells and infiltration of CXCR6+ CD4+ Trm cells, with CD4 stem-like memory cells showing interferon responses rather than exhaustion. In IDH1 wildtype glioblastoma patients treated with neoadjuvant pembrolizumab, CD4+ Trm association with prolonged overall survival was confirmed.

    Why it matters: Identifies a T-cell subset that predicts checkpoint inhibitor response and survival in glioblastoma.

  6. bioRxiv Genomics40

    Identifying, phasing, and structurally annotating sex chromosomes for genome assemblies using CBS-tools

    CBS-tools is a k-mer based pipeline using whole-genome sequencing of a few sex-identified isolates to identify sex chromosomes in genome assemblies. It predicted the correct heterogametic sex in all 31 species tested from public datasets, verified and corrected phasing of sex chromosomes between haplotypes, and delimited the sex-determination region boundary via an interactive web platform. It works for both unexplored and well-examined sex chromosome systems.

    Why it matters: Validated method that automates sex chromosome identification, phasing and SDR annotation across 31 species.

  7. bioRxiv Genomics50

    Evolutionary dynamics of the insertion sequence IS6110 in the Mycobacterium tuberculosis complex

    Analysis of 10,000 Mycobacterium tuberculosis complex genomes, using a reference-free tool and ancestral state reconstruction, maps the evolutionary dynamics of insertion sequence IS6110. Copy numbers range from 1 in some clades to more than 30 in La3 (M. orygis), birth rates scale linearly with copy number, and the 5% most frequently targeted regions account for half of all independent insertion events. The authors propose a niche constraints model in which insertions accumulate where DNA properties suit the element and functional cost to the host is low.

    Why it matters: First genome-wide view of IS6110 dynamics across 10,000 MTBC strains, with a reference-free insertion-calling tool.

  8. bioRxiv Genomics37

    Alcohol Use Disorder and Smoking-Associated Molecular Alterations in Human Prefrontal Cortex in Single Nucleus (sn) RNA-Seq

    Single-nucleus RNA-seq of the human prefrontal cortex shows that alcohol use disorder and smoking, each limited to one or two excitatory-neuron subtypes on their own, spread neuroinflammatory, complement and proteostatic pathway changes across nearly all subtypes when they co-occur. The analysis covered 614,932 nuclei and 24 cell types from 73 individuals. Combined exposure also drove microglia into a phagocytosis-repressed, exhaustion-like state, with inflammatory signaling shifting to astrocytes and oligodendrocyte lineage cells.

    Why it matters: It maps cell-type-specific transcriptomic interactions of AUD and smoking in human cortex at unprecedented nuclei scale.

  9. bioRxiv Cancer Biology69

    Functional Deorphanization of Tumor-reactive TCRs Uncovers a Landscape of Shared, Immune Dominant Antigens across Cancers

    The TWISTAR platform deorphanizes single-cell-derived TCRs against tumor transcriptomes and directly validates TCR engagement, so it recovers only functionally immunogenic antigens. Applied to melanoma, breast, and hepatocellular carcinoma patients responding to immune checkpoint blockade, it shows tumor-reactive TCRs recognize many targets beyond neoantigens, including peptides from unannotated coding sequences and novel transcripts. Many antigens are shared across patients and cancer types, with multiple T cell clones converging on a few immune dominant epitopes, supporting pan-cancer vaccine development.

    Why it matters: Identifies shared, immune dominant tumor antigens beyond neoantigens, opening targets for pan-cancer vaccines.

Sep 29Tue
  1. bioRxiv Genomics61

    Genomic correlates of metastatic competence and progression in human melanoma

    Metastatic competence in primary cutaneous melanoma is marked by somatic copy-number alterations and chromosomal instability rather than oncogenic point mutations, which were largely shared between primaries and metastases. Sequencing of 247 stage I/II primary melanomas and 60 matched metastases with median followup of 92 months yielded OncoCycle, a six-gene copy-number signature that predicted relapse independently of clinicopathological features. Matched pairs showed progression driven by continued copy-number evolution, with both monoclonal and polyclonal seeding resolved by clonal reconstruction.

    Why it matters: A six-gene copy-number signature predicts melanoma relapse and reframes metastasis as copy-number driven.

  2. bioRxiv Cancer Biology60

    BRCA2 loss drives a PKM1-dominant glycolytic state that is selectively lethal to pyruvate kinase activation

    BRCA1/2 loss is linked to a PKM1-dominant glycolytic state with elevated pyruvate kinase activity, found across 10,619 TCGA tumors and isogenic BRCA1/2-deficient models. PKM activation with small-molecule activators, including the FDA-approved mitapivat, triggered superoxide accumulation, disrupted PINK1-dependent mitochondrial quality control, induced DNA damage, and selectively killed BRCA2-deficient tumors in vivo while sparing BRCA2-proficient counterparts. The work recasts homologous recombination deficiency as a metabolic state and identifies PKM activation as a candidate therapy for HR-deficient cancers.

    Why it matters: It turns HRD into a druggable metabolic vulnerability with an already FDA-approved activator.

  3. bioRxiv Cancer Biology53

    SMYD3 protein degraders in HPV-negative head and neck squamous cell carcinoma.

    SMYD3 PROTACs, unlike catalytic inhibitors that lack phenotypic efficacy, degrade SMYD3 and curb proliferation and invasion in HPV-negative HNSCC cell lines. The compound IAP-08 degrades SMYD3 with a DC50 of about 177 nM and Dmax of about 90%, forms ternary complexes with XIAP E3 ligase, and shows favorable pharmacokinetics in vivo. Degradation, but not enzymatic inhibition, reprograms cell cycle, EMT and type I IFN response genes, supporting clinical development of IAP-08 in a disease where SMYD3 is overexpressed in about 60% of tumors.

    Why it matters: It reframes SMYD3 as undruggable by inhibitors alone and provides a degrader with in vivo feasibility for HPV-negative HNSCC.

  4. bioRxiv Cancer Biology63

    SON-mediated circular RNA suppression promotes PKR signaling and radiation resistance in glioblastoma

    The splicing co-factor SON suppresses circular RNA biogenesis in glioblastoma, and its elevation in radiation-resistant GBM is linked to widespread circRNA loss. SON knockdown raised circRNA abundance and attenuated PKR/NFκB signaling, and overexpression of the SON-suppressed circUSP1 and circSUCO reduced PKR activation and selectively decreased clonogenic survival after irradiation in radiation-resistant cells, with little effect on parental cells. The work defines a SON/circRNA/PKR pathway and points to PKR-inhibitory circRNAs as tools to resensitize resistant GBM to radiotherapy.

    Why it matters: It identifies a specific SON/circRNA/PKR pathway behind acquired radiation resistance in glioblastoma.

  5. bioRxiv Cancer Biology58

    Epigenetic progression of pancreatic cancer to aggressive subtypes involves alternate routes of lineage reprogramming in subtype-intermediate progenitor cells

    Single-cell ATAC-seq of 33 primary tumors and 7 metastases from 39 PDAC patients, paired with 10 single-cell RNA-seq profiles, maps the cis-regulatory landscape underlying malignant cell state plasticity. GATA6+/KRT17+ co-accessibility marks a classical-basal subtype-intermediate progenitor state (SIP) with limited epigenetic reprogramming and better clinical outcomes. Classical tumors repressing basal accessibility activate neural-like progenitor and tuft lineage enhancers, while basal committed tumors show esophageal transdifferentiation, both with poorer outcomes and distinct immune and stromal phenotypes.

    Why it matters: Defines epigenetic lineage routes and a progenitor state that stratify PDAC outcomes and tumor microenvironment phenotypes.

  6. bioRxiv Cancer Biology57

    Early-life colonization by enterotoxigenic Bacteroides fragilis remodels gut epithelial stem cell states to drive colorectal cancer susceptibility

    Early-life colonization by enterotoxigenic Bacteroides fragilis (ETBF) remodels colonic epithelial stem cell states and drives colorectal cancer susceptibility. Neonatal ETBF exposure expanded Lgr5+ stem cells, enhanced Atoh1+ secretory differentiation, induced distal colon-specific Wnt hyperactivation, and increased precancerous lesions in ApcMin/+ mice. Non-toxigenic B. fragilis colonization in the same window prevented lesion formation, showing developmental context determines protection or predisposition.

    Why it matters: Defines a developmental window in which microbial toxin exposure imprints colorectal cancer risk in mice.

  7. bioRxiv Cancer Biology55

    Combining interstrand crosslinking agents with histone deacetylase inhibitors against high grade IDH mutant gliomas

    The interstrand crosslinking agent KL-50 retains antiproliferative activity against MMR-deficient IDHmut glioma models, where temozolomide GI values rose 2.2- to 30.4-fold, and extends median survival in BT142 orthotopic xenografts from 107.5 to 194 days. KL-50 plus the HDAC inhibitor belinostat shows synergistic cytotoxicity in BT142, 905, and TS603 cultures, with CRISPR screening implicating PKMYT1 as a determinant of sensitivity. The work offers a preclinical route past MMR-associated TMZ resistance.

    Why it matters: Provides a preclinical option for IDHmut gliomas with MMR-associated temozolomide resistance.

Sep 28Mon
  1. bioRxiv Cancer Biology54

    Transcriptional networks underlying tumour plasticity in small-cell lung cancer

    Single-cell multi-omics of small-cell lung cancer resolved distinct cell states along the neuroendocrine-to-nonneuroendocrine axis, including a previously unrecognised Intermediate state of low-identity immunogenic cells that serves as an obligatory route in lineage transition. A Boolean Bayes model of transcription factor networks (BoBa-T) predicted state regulators, and RORB was validated as a gatekeeper of the neuroendocrine state: its inactivation pushes NE cells into the Intermediate state, upregulates immunogenic programs, and inhibits tumour growth in immunocompetent hosts.

    Why it matters: Identifies an obligatory immunogenic intermediate state and RORB as a druggable gatekeeper of SCLC lineage plasticity.

  2. bioRxiv Cancer Biology64

    m6A-Driven Intratumoral Cholesterol Biosynthesis Fuels Castration-Resistant Prostate Cancer Progression

    A METTL3–NUP93 interaction couples m6A-mediated nuclear mRNA export to cholesterol biosynthesis, driving castration-resistant prostate cancer. Overexpression of wild-type METTL3 or NUP93, but not enzymatically dead METTL3 or the METTL3-interaction-deficient NUP93 mutant, raised intracellular androgens, activated AR signaling under castrate conditions, and promoted androgen-independent growth in vitro and in vivo. Pharmacological inhibition of METTL3 or targeted demethylation of mRNAs encoding cholesterol biosynthesis enzymes suppressed CRPC malignancy.

    Why it matters: Identifies a druggable m6A-METTL3-NUP93 axis linking mRNA export to androgen production in CRPC.

  3. bioRxiv Cancer Biology67

    Disruption of the ARID1A-containing SWI/SNF complex reprograms tumor-associated macrophages and enhances immunotherapy response

    Disrupting the SWI/SNF chromatin remodeling complex in tumor-associated macrophages reprograms them and improves checkpoint blockade immunotherapy. Pharmacologic inhibition of SWI/SNF ATPase activity slowed tumor growth, and deleting the SWI/SNF subunit Arid1a in myeloid cells was sufficient to suppress tumor progression and enhance checkpoint blockade response. The reprogramming involved reduced enhancer accessibility at poor-prognosis genes such as Spp1, increased accessibility at interferon-stimulated gene promoters, elevated CD86, and required CD86 costimulation and CD8+ T cells.

    Why it matters: It identifies a druggable epigenetic target in macrophages that improves checkpoint blockade response.

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