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Comment
. 2020 Jul;16(7):e9757.
doi: 10.15252/msb.20209757.

The Cancer Dependency Map enables drug mechanism-of-action investigations

Francisca Vazquez  1 , Jesse S Boehm  1
Affiliations
Comment

The Cancer Dependency Map enables drug mechanism-of-action investigations

Francisca Vazquez et al. Mol Syst Biol. 2020 Jul.

Abstract

How do small molecules exert their effects in mammalian cells? This seemingly simple question continues to represent one of the fundamental challenges of modern translational science and as such has long been the subject of intense scientific scrutiny. In their recent study, Garnett and colleagues (Gonçalves et al, 2020) demonstrate proof-of-concept for a new way to attack this problem systematically for Oncology drugs, by identifying correlated CRISPR- and drug-killing profiles in the Cancer Dependency Map dataset.

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Figures

Figure 1
Figure 1. Using the Cancer Dependency Map data to generate MoA hypotheses
(A) By profiling hundreds of patient models of human cancer, the Cancer Dependency Map systematically identifies gene dependencies, small molecule sensitivities, and the markers that predict their response. (B) Correlations of genetic dependencies and drug sensitivities across cell lines can inform small molecule target(s) identification and mechanism‐of‐action. Red bars: cell killing; blue bars: no cell killing.
See this image and copyright information in PMC

Comment on

  • Drug mechanism-of-action discovery through the integration of pharmacological and CRISPR screens.
    Gonçalves E, Segura-Cabrera A, Pacini C, Picco G, Behan FM, Jaaks P, Coker EA, van der Meer D, Barthorpe A, Lightfoot H, Mironenko T, Beck A, Richardson L, Yang W, Lleshi E, Hall J, Tolley C, Hall C, Mali I, Thomas F, Morris J, Leach AR, Lynch JT, Sidders B, Crafter C, Iorio F, Fawell S, Garnett MJ. Gonçalves E, et al. Mol Syst Biol. 2020 Jul;16(7):e9405. doi: 10.15252/msb.20199405. Mol Syst Biol. 2020. PMID: 32627965 Free PMC article.

References

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    1. Gonçalves E, Segura‐Cabrera A, Pacini C, Picco G, Behan F, Jaaks P, Coker EA, Van der Meer D, Barthorpe A, Lightfoot H et al (2020) Drug mechanism‐of‐action discovery through the integration of pharmacological and CRISPR screens. Mol Syst Biol 16: e9405 10.15252/msb.20199405 - DOI - PMC - PubMed

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