{"doi":"10.1101/2025.08.27.672618","title":"LOX inhibition disrupts a collagen-integrin–MYC axis as a translatable targeting strategy in invasive lobular carcinoma","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Invasive lobular carcinoma (ILC) accounts for 15% of breast cancers yet lacks specific therapy because ILCs are underrepresented in clinical trials and preclinical models are lacking. We established intraductal xenograft models to test whether the clinical pan-lysyl-oxidase PXS-5505, now in phase trials for myelofibrosis can exploit the collagen-rich matrix dependency created by CDH1 loss. PXS-5505 remodels fibrillar collagen, and halts tumor expansion and metastatic seeding across ER+ and triple negative models without systemic toxicity. Genome-wide CRISPR screens reveal\n                  <jats:italic>ITGAV</jats:italic>\n                  and\n                  <jats:italic>ITGB5</jats:italic>\n                  as synthetic lethal partners of\n                  <jats:italic>CDH1</jats:italic>\n                  and LOX inhibition downregulates their expression together with MYC, NF-κB, and AP-1 transcriptional programmes. Collagen fibre density/alignment, and MYC/AP-1 gene signatures serve as pharmacodynamic readouts of drug activity. These data uncover a tractable ECM-integrin-MYC axis in ILC and nominate PXS-5505, alone or with endocrine therapy, for window of opportunity trials in this understudied breast cancer subtype.\n                </jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary</jats:title>\n                  <jats:p>Targeting matrix remodelling in ILC inhibits ILC progression and alters multiple molecular endpoints, providing a translatable therapeutic strategy for this understudied subtype that requires better treatments.</jats:p>\n                </jats:sec>","journal":null,"year":null,"id":640066,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"LOX inhibition disrupts a collagen-integrin–MYC axis as a translatable targeting strategy in invasive lobular carcinoma","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Invasive lobular carcinoma (ILC) accounts for 15% of breast cancers yet lacks specific therapy because ILCs are underrepresented in clinical trials and preclinical models are lacking. We established intraductal xenograft models to test whether the clinical pan-lysyl-oxidase PXS-5505, now in phase trials for myelofibrosis can exploit the collagen-rich matrix dependency created by CDH1 loss. PXS-5505 remodels fibrillar collagen, and halts tumor expansion and metastatic seeding across ER+ and triple negative models without systemic toxicity. Genome-wide CRISPR screens reveal\n                  <jats:italic>ITGAV</jats:italic>\n                  and\n                  <jats:italic>ITGB5</jats:italic>\n                  as synthetic lethal partners of\n                  <jats:italic>CDH1</jats:italic>\n                  and LOX inhibition downregulates their expression together with MYC, NF-κB, and AP-1 transcriptional programmes. Collagen fibre density/alignment, and MYC/AP-1 gene signatures serve as pharmacodynamic readouts of drug activity. These data uncover a tractable ECM-integrin-MYC axis in ILC and nominate PXS-5505, alone or with endocrine therapy, for window of opportunity trials in this understudied breast cancer subtype.\n                </jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary</jats:title>\n                  <jats:p>Targeting matrix remodelling in ILC inhibits ILC progression and alters multiple molecular endpoints, providing a translatable therapeutic strategy for this understudied subtype that requires better treatments.</jats:p>\n                </jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W4413904262","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/09/01/2025.08.27.672618.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2025/09/01/2025.08.27.672618.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2025.08.27.672618","host_type":"publisher"},{"url":"https://doi.org/10.1101/2025.08.27.672618","host_type":"repository"}],"fields_of_study":["Cell Adhesion Molecules Research","Angiogenesis and VEGF in Cancer","Inflammatory mediators and NSAID effects"],"mesh_terms":[],"keywords":["Integrin","Cancer research","Invasive lobular carcinoma","Pathology","Chemistry","Medicine","Internal medicine","Receptor","Cancer","Breast cancer","Invasive ductal carcinoma","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T06:01:24.226633Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}