ArticleNature cancer2023
A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer.
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Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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93citing papers in PubMed, 1 pooled it
17.1field-weighted citation impact, top 1% of its field
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Bibliometric analysis combined with visualization on universal trends and hot topics of LOX family in human diseases: 1995 to 2025.Frontiers in oncology · 2025Pooled it
- A phase I/IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis.Haematologica · 2025Trial
- Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026Review
- FAK Mediated Coordination of Extracellular Matrix Remodeling and Cellular Mechanics Impairs Nanomedicine Delivery in Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic reprogramming in cancer-associated fibroblasts: orchestrating the tumor immune microenvironment and response to immune checkpoint blockade.Experimental hematology & oncology · 2026Review
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- Dual Functions of B7-H3-MAPK Signaling Orchestrate Tumor Immunosuppression via Regulating the Plasticity of Myeloid-derived Suppressor Cells and Fibroblasts.Cancer discovery · 2026Article
- Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC.Cell reports. Medicine · 2026Article
- Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma.Cells · 2026Review
- Desmoplasia and therapeutic resistance in pancreatic ductal adenocarcinoma.Cancer letters · 2026Review
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- RaFiST: a radiomics model for non-invasive stratification of tumor fibrosis and prognostic prediction in non-small cell lung cancer.European radiology · 2026Article
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Review
- Mechanical regulation of immunity in metastasis.Nature materials · 2026Article
- Collagen-derived biomarkers reveal distinct fibrotic responses among cancer-associated fibroblasts.Scientific reports · 2026Article
- Glutamine-dependent changes in fibroblast-derived extracellular matrix dictate cancer cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Identification of Pancreatic Ductal Adenocarcinoma Extracellular Matrix Signatures from In-Depth Proteomic Profiling that Correlate with Lymphocyte Infiltration.Cancer research communications · 2026Article
- A targetable opioid/cancer associated fibroblast axis drives extracellular matrix remodeling and tumor aggressiveness in pancreatic cancer.bioRxiv : the preprint server for biology · 2026Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
54 authors at 20 institutions in 4 countries.
Jessica L ChittyCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0003-1776-1618
Michelle Yam *Cancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Lara Perryman *Pharmaxis, Frenchs Forest, New South Wales, Australia.
Amelia L ParkerCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Joanna N SkhinasCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Yordanos F I SetargewCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Ellie T Y MokCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Emmi TranCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Rhiannon D GrantCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0002-7674-5223
Sharissa L LathamSchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-1128-5315
Brooke A PereiraSchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Shona C RitchieThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Kendelle J MurphySchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Michael TrpceskiSchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Alison D FindlayPharmaxis, Frenchs Forest, New South Wales, Australia.
Pauline MelenecThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Elysse C FilipeCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Audrey NadaliniCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0009-0007-8779-8447
Sipiththa VelayutharCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Gretel MajorCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0002-4275-4199
Kaitlin WyllieCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Michael PapanicolaouCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0002-7998-3171
Shivanjali RatnaseelanCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Phoebe A PhillipsSchool of Biomedical Sciences, Faculty of Medicine, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-4481-8782
George SharbeenSchool of Biomedical Sciences, Faculty of Medicine, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.
Janet YoukhanaSchool of Biomedical Sciences, Faculty of Medicine, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.
Alice RussoThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Antonia BlackwellThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0009-0004-8799-8885
Jordan F HastingsThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Morghan C LucasThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Cecilia R ChambersThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Daniel A ReedThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0002-3736-7725
Janett StoehrThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Claire VenninThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Ruth PidsleySchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Anaiis ZaratzianThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Andrew M Da SilvaThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Michael TayaoThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Brett CharltonPharmaxis, Frenchs Forest, New South Wales, Australia.
David HerrmannCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0002-9514-7501
Max NobisSchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Susan J ClarkSchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
Andrew V BiankinWolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-0362-5597
Amber L JohnsThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
David R CroucherSchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-4965-8674
Adnan NagrialDepartment of Medical Oncology, Westmead Hospital, Sydney, New South Wales, Australia.
Anthony J GillThe Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
Sean M GrimmondUniversity of Melbourne Centre for Cancer Research, VCCC, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-8102-7998
Australian Pancreatic Cancer Genome Initiative (APGI)
Australian Pancreatic Cancer Matrix Atlas (APMA)
Marina PajicSchool of Clinical Medicine, St Vincent's Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-3871-3829
Paul TimpsonCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.ORCID http://orcid.org/0000-0002-5514-7080
Wolfgang JarolimekPharmaxis, Frenchs Forest, New South Wales, Australia. wolfgang.jarolimek@pharmaxis.com.au.ORCID http://orcid.org/0000-0002-1757-5420
Thomas R CoxCancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia. t.cox@garvan.org.au.ORCID http://orcid.org/0000-0001-9294-1745
Garvan Institute of Medical Research · AUQIMR Berghofer Medical Research Institute · AUPrincess Alexandra Hospital · AUSt John of God Subiaco Hospital · AUUniversity of Verona · ITPharmaxis (Australia) · AURoyal Adelaide Hospital · AURoyal North Shore Hospital · AURoyal Prince Alfred Hospital · AUBankstown Lidcombe Hospital · AUFlinders Medical Centre · AUFremantle Hospital · AUThe University of Melbourne · AUUNSW Sydney · AUWestmead Hospital · AUAustin Hospital · AULiverpool Hospital · AUSt Vincent's Hospital Sydney · AUGlasgow Royal Infirmary · GBPrince of Wales Hospital · AU
Funding
Cancer Research UK 25813
Abstract
The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-5505, a first-in-class highly selective and potent pan-lysyl oxidase inhibitor. We demonstrate in vitro and in vivo that pan-lysyl oxidase inhibition decreases chemotherapy-induced pancreatic tumor desmoplasia and stiffness, reduces cancer cell invasion and metastasis, improves tumor perfusion and enhances the efficacy of chemotherapy in the autochthonous genetically engineered KPC model, while also demonstrating antifibrotic effects in human patient-derived xenograft models of pancreatic cancer. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues. Our findings present the rationale for progression of a pan-lysyl oxidase inhibitor aimed at eliciting a reduction in stromal matrix to potentiate chemotherapy in pancreatic ductal adenocarcinoma.
Indexed as
Pancreatic DiseasesPancreatic NeoplasmsGemcitabineHumansProtein-Lysine 6-OxidaseGemcitabineProtein-Lysine 6-Oxidase
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.