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DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

by Figueiredo, Ines , Omlin, Aurelius , Perez-Lopez, Raquel , Jain, Suneil , A’Hern, Roger , Robinson, Dan , Eeles, Rosalind , Porta, Nuria , Chinnaiyan, Arul M , Kunju, Lakshmi P , Ralph, Christy , de Bono, Johann S , Brough, Rachel , Tunariu, Nina , Mateo, Joaquin , Flohr, Penny , Sandhu, Shahneen , Goodall, Jane , Wu, Yi-Mi , Williamson, Chris T , Attard, Gerhardt , Paulding, Claire , Mossop, Helen , Rubin, Mark A , Knudsen, Karen E , Ferraldeschi, Roberta , Fowler, Gemma , Nava Rodrigues, Daniel , Jones, Robert , McGovern, Ursula , Pemberton, Helen , Swain, Amanda , Gillman, Alexa , Hall, Emma , Hussain, Syed , Riisnaes, Ruth , Bianchini, Diletta , Miranda, Susana , Protheroe, Andrew , Zafeiriou, Zafeiris , Ashworth, Alan , Feng, Felix Y , Yuan, Wei , Cao, Xuhong , Elliott, Tony , Ebbs, Bernardette , Seed, George , Lord, Christopher J , Carreira, Suzanne , Roda, Desamparados , Boysen, Gunther

in Adenosine / Adult / Aged / Anemia / Anemia - chemically induced / Antineoplastic Agents - therapeutic use / Ataxia Telangiectasia Mutated Proteins - genetics / BRCA1 protein / BRCA2 protein / Castration / DNA repair / DNA Repair - genetics / DNA sequencing / Drug Resistance, Neoplasm / Enzyme Inhibitors - adverse effects / Enzyme Inhibitors - therapeutic use / Fatigue / Fatigue - chemically induced / Gene expression / Genes, BRCA2 / Genes, Tumor Suppressor / Humans / Inhibitor drugs / Male / Metastases / Metastasis / Middle Aged / Molecular biology / Mutation / Neoplasm Metastasis - drug therapy / Patients / Phthalazines - adverse effects / Phthalazines - therapeutic use / Piperazines - adverse effects / Piperazines - therapeutic use / Poly(ADP-ribose) polymerase / Poly(ADP-ribose) Polymerase Inhibitors / Prostate cancer / Prostate-specific antigen / Prostatic Neoplasms - drug therapy / Prostatic Neoplasms - genetics / Prostatic Neoplasms - pathology / Ribose / Solid tumors / Tablets

2015

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DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

2015

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2015

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Journal Article

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

Figueiredo, Ines,

Omlin, Aurelius,

Perez-Lopez, Raquel,

Jain, Suneil,

A’Hern, Roger,

Robinson, Dan,

Eeles, Rosalind,

Porta, Nuria,

Chinnaiyan, Arul M,

Kunju, Lakshmi P,

Ralph, Christy,

de Bono, Johann S,

Brough, Rachel,

Tunariu, Nina,

Mateo, Joaquin,

Flohr, Penny,

Sandhu, Shahneen,

Goodall, Jane,

Wu, Yi-Mi,

Williamson, Chris T,

Attard, Gerhardt,

Paulding, Claire,

Mossop, Helen,

Rubin, Mark A,

Knudsen, Karen E,

Ferraldeschi, Roberta,

Fowler, Gemma,

Nava Rodrigues, Daniel,

Jones, Robert,

McGovern, Ursula,

Pemberton, Helen,

Swain, Amanda,

Gillman, Alexa,

Hall, Emma,

Hussain, Syed,

Riisnaes, Ruth,

Bianchini, Diletta,

Miranda, Susana,

Protheroe, Andrew,

Zafeiriou, Zafeiris,

Ashworth, Alan,

Feng, Felix Y,

Yuan, Wei,

Cao, Xuhong,

Elliott, Tony,

Ebbs, Bernardette,

Seed, George,

Lord, Christopher J,

Carreira, Suzanne,

Roda, Desamparados,

Boysen, Gunther

2015

Overview

Fourteen of 16 patients with metastatic, castration-resistant prostate cancer and genetic defects in repair of DNA damage had a response to the PARP inhibitor olaparib. Anemia and fatigue were the major toxic effects. Prostate cancer is the most common cancer in men and the sixth leading cause of death from cancer among men throughout the world. 1 The interpatient molecular heterogeneity of this disease is well recognized; however, treatment to date has not been molecularly stratified. 2 , 3 It would be useful to identify predictive biomarkers in order to provide more precise treatment for this disease. 4 Metastatic, castration-resistant prostate cancer can have genomic aberrations that interfere with DNA repair. 3 , 5 Some of these aberrations have been associated with sensitivity to platinum and poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors, suggesting that treatment with a PARP inhibitor . . .

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Publisher

Massachusetts Medical Society

Subject

Adenosine

/ Adult

/ Aged

/ Anemia

/ Anemia - chemically induced

/ Antineoplastic Agents - therapeutic use

/ Ataxia Telangiectasia Mutated Proteins - genetics