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Drug response profi...
Drug response profiles in patient-derived cancer cells across histological subtypes of ovarian cancer: real-time therapy tailoring for a patient with low-grade serous carcinoma
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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2022-12-07
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Springer Science and Business Media LLC,2023
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:151462744
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http://kipublications.ki.se/Default.aspx?queryparsed=id:151462744URI
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https://doi.org/10.1038/s41416-022-02067-zDOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Many efforts are underway to develop novel therapies against the aggressive high-grade serous ovarian cancers (HGSOCs), while our understanding of treatment options for low-grade (LGSOC) or mucinous (MUCOC) of ovarian malignancies is not developing as well. We describe here a functional precision oncology (fPO) strategy in epithelial ovarian cancers (EOC), which involves high-throughput drug testing of patient-derived ovarian cancer cells (PDCs) with a library of 526 oncology drugs, combined with genomic and transcriptomic profiling. HGSOC, LGSOC and MUCOC PDCs had statistically different overall drug response profiles, with LGSOCs responding better to targeted inhibitors than HGSOCs. We identified several subtype-specific drug responses, such as LGSOC PDCs showing high sensitivity to MDM2, ERBB2/EGFR inhibitors, MUCOC PDCs to MEK inhibitors, whereas HGSOCs showed strongest effects with CHK1 inhibitors and SMAC mimetics. We also explored several drug combinations and found that the dual inhibition of MEK and SHP2 was synergistic in MAPK-driven EOCs. We describe a clinical case study, where real-time fPO analysis of samples from a patient with metastatic, chemorefractory LGSOC with a CLU-NRG1 fusion guided clinical therapy selection. fPO-tailored therapy with afatinib, followed by trastuzumab and pertuzumab, successfully reduced tumour burden and blocked disease progression over a five-year period. In summary, fPO is a powerful approach for the identification of systematic drug response differences across EOC subtypes, as well as to highlight patient-specific drug regimens that could help to optimise therapies to individual patients in the future.
Added entries (persons, corporate bodies, meetings, titles ...)
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Ungureanu, D
(author)
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Khan, S
(author)
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Arjama, M
(author)
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Valimaki, K
(author)
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Ianevski, A
(author)
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Ianevski, P
(author)
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Bergstrom, RKarolinska Institutet
(author)
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Dini, A
(author)
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Kanerva, A
(author)
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Koivisto-Korander, R
(author)
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Tapper, J
(author)
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Lassus, H
(author)
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Loukovaara, M
(author)
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Magi, A
(author)
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Hirasawa, A
(author)
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Aoki, D
(author)
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Pietiainen, V
(author)
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Pellinen, T
(author)
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Butzow, R
(author)
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Aittokallio, T
(author)
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Kallioniemi, OKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:British journal of cancer: Springer Science and Business Media LLC128:4, s. 678-6901532-18270007-0920
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- By the author/editor
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Murumagi, A
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Ungureanu, D
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Khan, S
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Arjama, M
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Valimaki, K
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Ianevski, A
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show more...
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Ianevski, P
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Bergstrom, R
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Dini, A
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Kanerva, A
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Koivisto-Korande ...
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Tapper, J
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Lassus, H
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Loukovaara, M
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Magi, A
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Hirasawa, A
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Aoki, D
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Pietiainen, V
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Pellinen, T
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Butzow, R
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Aittokallio, T
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Kallioniemi, O
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British journal ...
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Karolinska Institutet