Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress

Michael D. Nyquist; Alexandra Corella; Ilsa Coleman; Navonil De Sarkar; Arja Kaipainen; Gavin Ha; Roman Gulati; Lisa Ang; Payel Chatterjee; Jared Lucas; Colin Pritchard; Gail Risbridger; John Isaacs; Bruce Montgomery; Colm Morrissey; Eva Corey; Peter S. Nelson

doi:10.1016/j.celrep.2020.107669

Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress

Michael D. Nyquist, Alexandra Corella, Ilsa Coleman, Navonil De Sarkar, Arja Kaipainen, Gavin Ha, Roman Gulati, Lisa Ang, Payel Chatterjee, Jared Lucas, Colin Pritchard, Gail Risbridger, John Isaacs, Bruce Montgomery, Colm Morrissey, Eva Corey, Peter S. Nelson

Anatomy & Developmental Biology

Research output: Contribution to journal › Article › Research › peer-review

92 Citations (Scopus)

Abstract

Nyquist et al. demonstrate that TP53 and RB1 loss in prostate carcinoma (PC) attenuates AR signaling and enhances cell proliferation but does not uniformly induce neuroendocrine phenotypes. PCs with TP53/RB1 loss resist a wide range of cancer therapeutics but respond to PARP and ATR inhibition, likely reflecting enhanced replication stress.

Original language	English
Article number	107669
Number of pages	23
Journal	Cell Reports
Volume	31
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2020.107669
Publication status	Published - 26 May 2020

Keywords

androgen receptor
antiandrogen
ATR
DNA damage
neuroendocrine
PARP
plasticity
prostate cancer
RB1
TP53

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2020.107669Licence: CC BY-NC-ND

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Nyquist, M. D., Corella, A., Coleman, I., De Sarkar, N., Kaipainen, A., Ha, G., Gulati, R., Ang, L., Chatterjee, P., Lucas, J., Pritchard, C., Risbridger, G., Isaacs, J., Montgomery, B., Morrissey, C., Corey, E., & Nelson, P. S. (2020). Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress. Cell Reports, 31(8), [107669]. https://doi.org/10.1016/j.celrep.2020.107669

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title = "Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress",

abstract = "Nyquist et al. demonstrate that TP53 and RB1 loss in prostate carcinoma (PC) attenuates AR signaling and enhances cell proliferation but does not uniformly induce neuroendocrine phenotypes. PCs with TP53/RB1 loss resist a wide range of cancer therapeutics but respond to PARP and ATR inhibition, likely reflecting enhanced replication stress.",

keywords = "androgen receptor, antiandrogen, ATR, DNA damage, neuroendocrine, PARP, plasticity, prostate cancer, RB1, TP53",

author = "Nyquist, {Michael D.} and Alexandra Corella and Ilsa Coleman and {De Sarkar}, Navonil and Arja Kaipainen and Gavin Ha and Roman Gulati and Lisa Ang and Payel Chatterjee and Jared Lucas and Colin Pritchard and Gail Risbridger and John Isaacs and Bruce Montgomery and Colm Morrissey and Eva Corey and Nelson, {Peter S.}",

year = "2020",

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Nyquist, MD, Corella, A, Coleman, I, De Sarkar, N, Kaipainen, A, Ha, G, Gulati, R, Ang, L, Chatterjee, P, Lucas, J, Pritchard, C, Risbridger, G, Isaacs, J, Montgomery, B, Morrissey, C, Corey, E & Nelson, PS 2020, 'Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress', Cell Reports, vol. 31, no. 8, 107669. https://doi.org/10.1016/j.celrep.2020.107669

TY - JOUR

T1 - Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress

AU - Nyquist, Michael D.

AU - Corella, Alexandra

AU - Coleman, Ilsa

AU - De Sarkar, Navonil

AU - Kaipainen, Arja

AU - Ha, Gavin

AU - Gulati, Roman

AU - Ang, Lisa

AU - Chatterjee, Payel

AU - Lucas, Jared

AU - Pritchard, Colin

AU - Risbridger, Gail

AU - Isaacs, John

AU - Montgomery, Bruce

AU - Morrissey, Colm

AU - Corey, Eva

AU - Nelson, Peter S.

PY - 2020/5/26

Y1 - 2020/5/26

N2 - Nyquist et al. demonstrate that TP53 and RB1 loss in prostate carcinoma (PC) attenuates AR signaling and enhances cell proliferation but does not uniformly induce neuroendocrine phenotypes. PCs with TP53/RB1 loss resist a wide range of cancer therapeutics but respond to PARP and ATR inhibition, likely reflecting enhanced replication stress.

AB - Nyquist et al. demonstrate that TP53 and RB1 loss in prostate carcinoma (PC) attenuates AR signaling and enhances cell proliferation but does not uniformly induce neuroendocrine phenotypes. PCs with TP53/RB1 loss resist a wide range of cancer therapeutics but respond to PARP and ATR inhibition, likely reflecting enhanced replication stress.

KW - androgen receptor

KW - antiandrogen

KW - ATR

KW - DNA damage

KW - neuroendocrine

KW - PARP

KW - plasticity

KW - prostate cancer

KW - RB1

KW - TP53

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U2 - 10.1016/j.celrep.2020.107669

DO - 10.1016/j.celrep.2020.107669

M3 - Article

C2 - 32460015

AN - SCOPUS:85085319793

VL - 31

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 8

M1 - 107669

ER -

Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress

Abstract

Keywords

UN SDGs

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