Abstract:
UNLABELLED:Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2). SIGNIFICANCE:We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses.
journal_name
Cancer Discovjournal_title
Cancer discoveryauthors
Seashore-Ludlow B,Rees MG,Cheah JH,Cokol M,Price EV,Coletti ME,Jones V,Bodycombe NE,Soule CK,Gould J,Alexander B,Li A,Montgomery P,Wawer MJ,Kuru N,Kotz JD,Hon CS,Munoz B,Liefeld T,Dančík V,Bittker JA,Palmer M,doi
10.1158/2159-8290.CD-15-0235subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1210-23issue
11eissn
2159-8274issn
2159-8290pii
2159-8290.CD-15-0235journal_volume
5pub_type
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