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Comment
. 2021 May;11(5):1011-1013.
doi: 10.1158/2159-8290.CD-21-0184.

Toppling the HAT to Treat Lethal Prostate Cancer

Reyaz Ur Rasool  1 , Ramakrishnan Natesan  1 , Irfan A Asangani  2   3
Affiliations
Comment

Toppling the HAT to Treat Lethal Prostate Cancer

Reyaz Ur Rasool et al. Cancer Discov. 2021 May.

Abstract

In this issue of Cancer Discovery, Welti and colleagues demonstrate a positive correlation between the expression of the histone acetyltransferase paralogs CBP and p300 with increased androgen receptor (AR) signaling and androgen deprivation therapy resistance in advanced prostate cancer. CCS1477, a selective inhibitor of p300/CBP bromodomain, disrupts AR- and MYC-regulated gene expression, suppresses tumor growth in vivo in multiple castration-resistant prostate cancer xenograft models, and modulates biomarker expression in early clinical evaluation, providing a novel therapeutic approach for AR-addicted advanced prostate cancer.See related article by Welti et al., p. 1118.

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Comment on

  • Targeting the p300/CBP Axis in Lethal Prostate Cancer.
    Welti J, Sharp A, Brooks N, Yuan W, McNair C, Chand SN, Pal A, Figueiredo I, Riisnaes R, Gurel B, Rekowski J, Bogdan D, West W, Young B, Raja M, Prosser A, Lane J, Thomson S, Worthington J, Onions S, Shannon J, Paoletta S, Brown R, Smyth D, Harbottle GW, Gil VS, Miranda S, Crespo M, Ferreira A, Pereira R, Tunariu N, Carreira S, Neeb AJ, Ning J, Swain A, Taddei D; SU2C/PCF International Prostate Cancer Dream Team; Schiewer MJ, Knudsen KE, Pegg N, de Bono JS. Welti J, et al. Cancer Discov. 2021 May;11(5):1118-1137. doi: 10.1158/2159-8290.CD-20-0751. Epub 2021 Jan 11. Cancer Discov. 2021. PMID: 33431496 Free PMC article.

References

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    1. Natesan R, Aras S, Effron SS, Asangani IA. Epigenetic regulation of chromatin in prostate cancer. Adv Exp Med Biol. 2019;1210:379–407.
    1. Lasko LM, Jakob CG, Edalji RP, Qiu W, Montgomery D, Digiammarino EL, et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017;550:128–32.
    1. Jin L, Garcia J, Chan E, de la Cruz C, Segal E, Merchant M, et al. Therapeutic targeting of the CBP/p300 bromodomain blocks the growth of castration-resistant prostate cancer. Cancer Res. 2017;77:5564–75.