onr:"swepub:oai:prod.swepub.kib.ki.se:146827198"
Search: onr:"swepub:oai:prod.swepub.kib.ki.se:146827198" > Predicting ROR1/BCL...
- 1 of 1
- Previous record
- Next record
- To hitlist
Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung
- Wang, WZ (author)
- Shilo, K (author)
- Amann, JM (author)
- show more...
- Shulman, A (author)
- Schultz, J (author)
- Croce, CM (author)
- Carbone, DP (author)
- show less...
- (creator_code:org_t)
- 2021-06-04
- 2021
- English.
- In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:6, s. 577-
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Small cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
- Cell death & disease (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Wang, WZ
- Shilo, K
- Amann, JM
- Shulman, A
- Hojjat-Farsangi, ...
- Mellstedt, H
- show more...
- Schultz, J
- Croce, CM
- Carbone, DP
- show less...
- Articles in the publication
- Cell death & dis ...
- By the university
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
