ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer

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Standard

ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer. / Zhou, Yuzhen; Börcsök, Judit; Adib, Elio; Kamran, Sophia C.; Neil, Alexander J.; Stawiski, Konrad; Freeman, Dory; Stormoen, Dag Rune; Sztupinszki, Zsofia; Samant, Amruta; Nassar, Amin; Bekele, Raie T.; Hanlon, Timothy; Valentine, Henkel; Epstein, Ilana; Sharma, Bijaya; Felt, Kristen; Abbosh, Philip; Wu, Chin Lee; Efstathiou, Jason A.; Miyamoto, David T.; Anderson, William; Szallasi, Zoltan; Mouw, Kent W.

I: Science Advances, Bind 9, Nr. 47, eadg2263, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Zhou, Y, Börcsök, J, Adib, E, Kamran, SC, Neil, AJ, Stawiski, K, Freeman, D, Stormoen, DR, Sztupinszki, Z, Samant, A, Nassar, A, Bekele, RT, Hanlon, T, Valentine, H, Epstein, I, Sharma, B, Felt, K, Abbosh, P, Wu, CL, Efstathiou, JA, Miyamoto, DT, Anderson, W, Szallasi, Z & Mouw, KW 2023, 'ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer', Science Advances, bind 9, nr. 47, eadg2263. https://doi.org/10.1126/sciadv.adg2263

APA

Zhou, Y., Börcsök, J., Adib, E., Kamran, S. C., Neil, A. J., Stawiski, K., Freeman, D., Stormoen, D. R., Sztupinszki, Z., Samant, A., Nassar, A., Bekele, R. T., Hanlon, T., Valentine, H., Epstein, I., Sharma, B., Felt, K., Abbosh, P., Wu, C. L., ... Mouw, K. W. (2023). ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer. Science Advances, 9(47), [eadg2263]. https://doi.org/10.1126/sciadv.adg2263

Vancouver

Zhou Y, Börcsök J, Adib E, Kamran SC, Neil AJ, Stawiski K o.a. ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer. Science Advances. 2023;9(47). eadg2263. https://doi.org/10.1126/sciadv.adg2263

Author

Zhou, Yuzhen ; Börcsök, Judit ; Adib, Elio ; Kamran, Sophia C. ; Neil, Alexander J. ; Stawiski, Konrad ; Freeman, Dory ; Stormoen, Dag Rune ; Sztupinszki, Zsofia ; Samant, Amruta ; Nassar, Amin ; Bekele, Raie T. ; Hanlon, Timothy ; Valentine, Henkel ; Epstein, Ilana ; Sharma, Bijaya ; Felt, Kristen ; Abbosh, Philip ; Wu, Chin Lee ; Efstathiou, Jason A. ; Miyamoto, David T. ; Anderson, William ; Szallasi, Zoltan ; Mouw, Kent W. / ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer. I: Science Advances. 2023 ; Bind 9, Nr. 47.

Bibtex

@article{963938d9cd0c4f4bb9d43c3d6a529017,

title = "ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer",

abstract = "Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair–targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss alters the immune microenvironment and improves anti-PD1 response in preclinical bladder models but is not associated with improved anti-PD1/PD-L1 response in clinical cohorts. Last, we show that ATM expression by immunohistochemistry is strongly correlated with response to chemoradiotherapy. Together, these data define a potential role for ATM as a predictive biomarker in bladder cancer.",

author = "Yuzhen Zhou and Judit B{\"o}rcs{\"o}k and Elio Adib and Kamran, {Sophia C.} and Neil, {Alexander J.} and Konrad Stawiski and Dory Freeman and Stormoen, {Dag Rune} and Zsofia Sztupinszki and Amruta Samant and Amin Nassar and Bekele, {Raie T.} and Timothy Hanlon and Henkel Valentine and Ilana Epstein and Bijaya Sharma and Kristen Felt and Philip Abbosh and Wu, {Chin Lee} and Efstathiou, {Jason A.} and Miyamoto, {David T.} and William Anderson and Zoltan Szallasi and Mouw, {Kent W.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved;",

year = "2023",

doi = "10.1126/sciadv.adg2263",

language = "English",

volume = "9",

journal = "Science advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "47",

}

RIS

TY - JOUR

T1 - ATM deficiency confers specific therapeutic vulnerabilities in bladder cancer

AU - Zhou, Yuzhen

AU - Börcsök, Judit

AU - Adib, Elio

AU - Kamran, Sophia C.

AU - Neil, Alexander J.

AU - Stawiski, Konrad

AU - Freeman, Dory

AU - Stormoen, Dag Rune

AU - Sztupinszki, Zsofia

AU - Samant, Amruta

AU - Nassar, Amin

AU - Bekele, Raie T.

AU - Hanlon, Timothy

AU - Valentine, Henkel

AU - Epstein, Ilana

AU - Sharma, Bijaya

AU - Felt, Kristen

AU - Abbosh, Philip

AU - Wu, Chin Lee

AU - Efstathiou, Jason A.

AU - Miyamoto, David T.

AU - Anderson, William

AU - Szallasi, Zoltan

AU - Mouw, Kent W.

PY - 2023

Y1 - 2023

N2 - Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair–targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss alters the immune microenvironment and improves anti-PD1 response in preclinical bladder models but is not associated with improved anti-PD1/PD-L1 response in clinical cohorts. Last, we show that ATM expression by immunohistochemistry is strongly correlated with response to chemoradiotherapy. Together, these data define a potential role for ATM as a predictive biomarker in bladder cancer.

AB - Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair–targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss alters the immune microenvironment and improves anti-PD1 response in preclinical bladder models but is not associated with improved anti-PD1/PD-L1 response in clinical cohorts. Last, we show that ATM expression by immunohistochemistry is strongly correlated with response to chemoradiotherapy. Together, these data define a potential role for ATM as a predictive biomarker in bladder cancer.

U2 - 10.1126/sciadv.adg2263

DO - 10.1126/sciadv.adg2263

M3 - Journal article

C2 - 37992168

AN - SCOPUS:85177976566

VL - 9

JO - Science advances

JF - Science advances

SN - 2375-2548

IS - 47

M1 - eadg2263

ER -

ID: 378951015