Abstract:
BACKGROUND:Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs. METHODS:We cultured and characterised patient-derived sarcoma cells and evaluated their sensitivity to 525 anti-cancer agents including both approved and non-approved drugs. In total, 14 sarcomas and 5 healthy mesenchymal primary cell cultures were studied. The sarcoma biopsies and derived cells were characterised by gene panel sequencing, cancer driver gene expression and by detecting specific fusion oncoproteins in situ in sarcomas with translocations. RESULTS:Soft tissue sarcoma cultures were established from patient biopsies with a success rate of 58%. The genomic profile and drug sensitivity testing on these samples helped to identify targeted inhibitors active on sarcomas. The cSrc inhibitor Dasatinib was identified as an active drug in sarcomas carrying chromosomal translocations. The drug sensitivity of the patient sarcoma cells ex vivo correlated with the response to the former treatment of the patient. CONCLUSIONS:Our results show that patient-derived sarcoma cells cultured in vitro are relevant and practical models for genotypic and phenotypic screens aiming to identify efficient drugs to treat sarcoma patients with poor treatment options.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Brodin BA,Wennerberg K,Lidbrink E,Brosjö O,Potdar S,Wilson JN,Ma L,Moens LN,Hesla A,Porovic E,Bernhardsson E,Papakonstantinou A,Bauer H,Tsagkozis P,von Sivers K,Wejde J,Östling P,Kallioniemi O,Stragliotto CLdoi
10.1038/s41416-018-0359-4subject
Has Abstractpub_date
2019-02-01 00:00:00pages
435-443issue
4eissn
0007-0920issn
1532-1827pii
10.1038/s41416-018-0359-4journal_volume
120pub_type
杂志文章abstract::Data obtained from multiple sources indicate that no single mechanism can explain the resistance to chemotherapy exhibited by non-small cell lung carcinomas. The multi-factorial nature of drug resistance implies that the analysis of comprising expression profiles may predict drug resistance with higher accuracy than s...
journal_title:British journal of cancer
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journal_title:British journal of cancer
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journal_title:British journal of cancer
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journal_title:British journal of cancer
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journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
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doi:10.1038/sj.bjc.6602234
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journal_title:British journal of cancer
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