A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors

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Fältnamn	Indikatorer	Metadata
000		04684naa a2200985 4500
001		oai:DiVA.org:su-158352
003		SwePub
008		180815s2018 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1583522 URI
024	7	a https://doi.org/10.1038/s41588-018-0138-42 DOI
040		a (SwePub)su
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Alvarez, Mariano J.4 aut
245	1 0	a A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors
264		c 2018-06-18
264	1	b Springer Science and Business Media LLC,c 2018
338		a print2 rdacarrier
520		a We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.
650	7	a NATURVETENSKAPx Biologi0 (SwePub)1062 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciences0 (SwePub)1062 hsv//eng
700	1	a Subramaniam, Prem S.4 aut
700	1	a Tang, Laura H.4 aut
700	1	a Grunn, Adina4 aut
700	1	a Aburi, Mahalaxmi4 aut
700	1	a Rieckhof, Gabrielle4 aut
700	1	a Komissarova, Elena V.4 aut
700	1	a Hagan, Elizabeth A.4 aut
700	1	a Bodei, Lisa4 aut
700	1	a Clemons, Paul A.4 aut
700	1	a Dela Cruz, Filemon S.4 aut
700	1	a Dhall, Deepti4 aut
700	1	a Diolaiti, Daniel4 aut
700	1	a Fraker, Douglas A.4 aut
700	1	a Ghavami, Afshin4 aut
700	1	a Kaemmerer, Daniel4 aut
700	1	a Karan, Charles4 aut
700	1	a Kidd, Mark4 aut
700	1	a Kim, Kyoung M.4 aut
700	1	a Kim, Hee C.4 aut
700	1	a Kunju, Lakshmi P.4 aut
700	1	a Langel, Ülou Stockholms universitet,Institutionen för neurokemi,University of Tartu, Estonia4 aut0 (Swepub:su)ulo
700	1	a Li, Zhong4 aut
700	1	a Lee, Jeeyun4 aut
700	1	a Li, Hai4 aut
700	1	a LiVolsi, Virginia4 aut
700	1	a Pfragner, Roswitha4 aut
700	1	a Rainey, Allison R.4 aut
700	1	a Realubit, Ronald B.4 aut
700	1	a Remotti, Helen4 aut
700	1	a Regberg, Jakobu Stockholms universitet,Institutionen för neurokemi4 aut
700	1	a Roses, Robert4 aut
700	1	a Rustgi, Anil4 aut
700	1	a Sepulveda, Antonia R.4 aut
700	1	a Serra, Stefano4 aut
700	1	a Shi, Chanjuan4 aut
700	1	a Yuan, Xiaopu4 aut
700	1	a Barberis, Massimo4 aut
700	1	a Bergamaschi, Roberto4 aut
700	1	a Chinnaiyan, Arul M.4 aut
700	1	a Detre, Tony4 aut
700	1	a Ezzat, Shereen4 aut
700	1	a Frilling, Andrea4 aut
700	1	a Hommann, Merten4 aut
700	1	a Jaeger, Dirk4 aut
700	1	a Kim, Michelle K.4 aut
700	1	a Knudsen, Beatrice S.4 aut
700	1	a Kung, Andrew L.4 aut
700	1	a Leahy, Emer4 aut
700	1	a Metz, David C.4 aut
700	1	a Milsom, Jeffrey W.4 aut
700	1	a Park, Young S.4 aut
700	1	a Reidy-Lagunes, Diane4 aut
700	1	a Schreiber, Stuart4 aut
700	1	a Washington, Kay4 aut
700	1	a Wiedenmann, Bertram4 aut
700	1	a Modlin, Irvin4 aut
700	1	a Califano, Andrea4 aut
710	2	a Stockholms universitetb Institutionen för neurokemi4 org
773	0	t Nature Geneticsd : Springer Science and Business Media LLCg 50:7, s. 979-989q 50:7<979-989x 1061-4036x 1546-1718
856	4	u https://europepmc.org/articles/pmc6421579?pdf=render
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-158352
856	4 8	u https://doi.org/10.1038/s41588-018-0138-4

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Av författaren/redakt...: Alvarez, Mariano ...; Subramaniam, Pre ...; Tang, Laura H.; Grunn, Adina; Aburi, Mahalaxmi; Rieckhof, Gabrie ...; visa fler...; Komissarova, Ele ...; Hagan, Elizabeth ...; Bodei, Lisa; Clemons, Paul A.; Dela Cruz, Filem ...; Dhall, Deepti; Diolaiti, Daniel; Fraker, Douglas ...; Ghavami, Afshin; Kaemmerer, Danie ...; Karan, Charles; Kidd, Mark; Kim, Kyoung M.; Kim, Hee C.; Kunju, Lakshmi P ...; Langel, Ülo; Li, Zhong; Lee, Jeeyun; Li, Hai; LiVolsi, Virgini ...; Pfragner, Roswit ...; Rainey, Allison ...; Realubit, Ronald ...; Remotti, Helen; Regberg, Jakob; Roses, Robert; Rustgi, Anil; Sepulveda, Anton ...; Serra, Stefano; Shi, Chanjuan; Yuan, Xiaopu; Barberis, Massim ...; Bergamaschi, Rob ...; Chinnaiyan, Arul ...; Detre, Tony; Ezzat, Shereen; Frilling, Andrea; Hommann, Merten; Jaeger, Dirk; Kim, Michelle K.; Knudsen, Beatric ...; Kung, Andrew L.; Leahy, Emer; Metz, David C.; Milsom, Jeffrey ...; Park, Young S.; Reidy-Lagunes, D ...; Schreiber, Stuar ...; Washington, Kay; Wiedenmann, Bert ...; Modlin, Irvin; Califano, Andrea; visa färre...

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Artiklar i publikationen: Nature Genetics

Av lärosätet: Stockholms universitet

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