{"doi":"10.3390/cancers16183133","title":"BRAF Inhibition and UVB Light Synergistically Promote Mus musculus Papillomavirus 1-Induced Skin Tumorigenesis","abstract":"The development of keratinocytic skin tumors, presumably attributable to paradoxical activation of the MAPK pathway, represents a relevant side effect of targeted therapies with BRAF inhibitors (BRAFis). The role of cutaneous papillomavirus infection in BRAFi-associated skin carcinogenesis, however, is still inconclusive. Employing the Mus musculus papillomavirus 1 (MmuPV1) skin infection model, the impact of BRAFis and UVB exposure on papillomavirus induced skin tumorigenesis was investigated in immunocompetent FVB/NCrl mice. Systemic BRAF inhibition in combination with UVB light induced skin tumors in 62% of the MmuPV1-infected animals. In contrast, significantly fewer tumors were observed in the absence of either BRAF inhibition, UVB irradiation or virus infection, as demonstrated by lesional outgrowth in 20%, 5% and 0% of the mice, respectively. Combinatory exposure to BRAFis and UVB favored productive viral infection, which was shown by high numbers of MmuPV1 genome copies and E1^E4 spliced transcripts and an abundance of E6/E7 oncogene mRNA and viral capsid proteins. BRAF inhibition, but not viral infection or UVB light, activated ERK1/2, whereas γH2AX expression, inducible by UVB light, remained unaltered by BRAFis. These results provide experimental evidence that BRAF inhibition and UVB irradiation synergistically promote MmuPV1-induced skin tumor development in vivo. This indicates an alternative pathway by which papillomavirus skin infection may contribute to BRAFi-associated skin tumorigenesis.","journal":"Cancers","year":2024,"id":503215,"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":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1352818,"name":"Julia Maria Ressler","orcid":"0000-0001-8602-0878","position":1,"is_corresponding":false},{"id":1352819,"name":"Katharina Riebenbauer","orcid":"0000-0001-5956-9478","position":2,"is_corresponding":false},{"id":1353147,"name":"Stefanie Kancz","orcid":null,"position":3,"is_corresponding":false},{"id":804253,"name":"Kim Purkhauser","orcid":"0000-0003-1732-9673","position":4,"is_corresponding":false},{"id":1353148,"name":"Victoria Bachmayr","orcid":null,"position":5,"is_corresponding":false},{"id":623636,"name":"Christophe Cataisson","orcid":"0000-0003-2600-1573","position":6,"is_corresponding":false},{"id":479570,"name":"Reinhard Kirnbauer","orcid":"0000-0002-5588-4179","position":7,"is_corresponding":false},{"id":1352820,"name":"Peter Petzelbauer","orcid":"0000-0001-7080-5259","position":8,"is_corresponding":false},{"id":1353149,"name":"Markus Wiesmueller","orcid":null,"position":9,"is_corresponding":false},{"id":1353150,"name":"Maximilian Egg","orcid":null,"position":10,"is_corresponding":false},{"id":275798,"name":"Christoph Höeller","orcid":"0000-0003-1192-0227","position":11,"is_corresponding":false},{"id":1352821,"name":"Alessandra Handisurya","orcid":"0000-0001-9823-7644","position":12,"is_corresponding":false},{"id":1352817,"name":"Sonja Dorfer","orcid":"0000-0001-8286-9620","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:10:27.781502Z","pmid":"39335105","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":[]}