Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer
Matti Annala,Matti Annala,Gillian Vandekerkhove,Daniel Khalaf,Sinja Taavitsainen,Kevin Beja,Evan W. Warner,Katherine Sunderland,Christian K. Kollmannsberger,Bernhard J. Eigl,Daygen Finch,Conrad D. Oja,Joanna Vergidis,Muhammad Zulfiqar,Arun Azad,Matti Nykter,Martin E. Gleave,Alexander W. Wyatt,Kim N. Chi,Kim N. Chi +19 more
TLDR
Although detection of AR amplifications did not outperform standard prognostic biomarkers, AR gene structural rearrangements truncating the ligand binding domain were identified in several patients with primary resistance and suggest that liquid biopsy analysis can guide the use of AR-targeted therapy in general practice.Abstract:
Primary resistance to androgen receptor (AR)-directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 patients with treatment-naive mCRPC to abiraterone or enzalutamide and performed whole-exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy. For these agents, which have never been directly compared, time to progression was similar. Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance. Somatic alterations in TP53, previously linked to reduced tumor dependency on AR signaling, were also independently associated with rapid resistance. Although detection of AR amplifications did not outperform standard prognostic biomarkers, AR gene structural rearrangements truncating the ligand binding domain were identified in several patients with primary resistance. These findings establish genomic drivers of resistance to first-line AR-directed therapy in mCRPC and identify potential minimally invasive biomarkers.Significance: Leveraging plasma specimens collected in a large randomized phase II trial, we report the relative impact of common circulating tumor DNA alterations on patient response to the most widely used therapies for advanced prostate cancer. Our findings suggest that liquid biopsy analysis can guide the use of AR-targeted therapy in general practice. Cancer Discov; 8(4); 444-57. ©2018 AACR.See related commentary by Jayaram et al., p. 392This article is highlighted in the In This Issue feature, p. 371.read more
Citations
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Genomic correlates of clinical outcome in advanced prostate cancer.
Wassim Abida,Joanna Cyrta,Joanna Cyrta,Glenn Heller,Davide Prandi,Joshua Armenia,Ilsa Coleman,Marcin Cieslik,Matteo Benelli,Dan R. Robinson,Eliezer M. Van Allen,Eliezer M. Van Allen,Andrea Sboner,Tarcisio Fedrizzi,Juan Miguel Mosquera,Brian D. Robinson,Navonil De Sarkar,Lakshmi P. Kunju,Scott A. Tomlins,Yi-Mi Wu,Daniel Nava Rodrigues,Massimo Loda,Massimo Loda,Anuradha Gopalan,Victor E. Reuter,Colin C. Pritchard,Joaquin Mateo,Diletta Bianchini,Susana Miranda,Suzanne Carreira,Pasquale Rescigno,Julie Filipenko,Jacob Vinson,Robert B. Montgomery,Himisha Beltran,Himisha Beltran,Elisabeth I. Heath,Howard I. Scher,Philip W. Kantoff,Mary-Ellen Taplin,Nikolaus Schultz,J. De-Bono,Francesca Demichelis,Peter S. Nelson,Mark A. Rubin,Mark A. Rubin,Arul M. Chinnaiyan,Charles L. Sawyers +47 more
TL;DR: This large analysis integrating mCRPC genomics with histology and clinical outcomes identifies RB1 genomic alteration as a potent predictor of poor outcome, and is a community resource for further interrogation of clinical and molecular associations.
Journal ArticleDOI
Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial
Ryan Phillips,William Shi,Matthew P. Deek,Noura Radwan,Su Jin Lim,Emmanuel S. Antonarakis,Steven P. Rowe,Ashley E. Ross,Michael A. Gorin,Curtiland Deville,Stephen Greco,Hailun Wang,Samuel R. Denmeade,Channing J. Paller,Shirl Dipasquale,Theodore L. DeWeese,Danny Y. Song,Hao Wang,Michael A. Carducci,Kenneth J. Pienta,Martin G. Pomper,Adam P. Dicker,Mario A. Eisenberger,Ash A. Alizadeh,Maximilian Diehn,Phuoc T. Tran +25 more
TL;DR: This randomized clinical trial assesses whether treatment with stereotactic ablative radiotherapy vs observation improves oncologic outcomes in men with recurrent hormone-sensitive oligometastatic prostate cancer.
Journal ArticleDOI
Treatment of Advanced Prostate Cancer
TL;DR: This work discusses advances in noncastrate disease states, identification of biomarkers for prognosis and treatment selection, and opportunities in locoregional therapy to delay androgen deprivation therapy.
Journal ArticleDOI
Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells
Laura Keller,Klaus Pantel +1 more
TL;DR: How circulate tumour cell (CTC) analysis at single-cell resolution provides unique insights into tumour heterogeneity that are not revealed by analysis of circulating tumour DNA (ctDNA) derived from liquid biopsies is discussed.
Journal ArticleDOI
Update on Systemic Prostate Cancer Therapies: Management of Metastatic Castration-resistant Prostate Cancer in the Era of Precision Oncology.
Philipp Nuhn,Johann S. de Bono,Karim Fizazi,Stephen J. Freedland,Stephen J. Freedland,Maurizio Grilli,Philip W. Kantoff,Guru Sonpavde,Cora N. Sternberg,Srinivasan Yegnasubramanian,Emmanuel S. Antonarakis +10 more
TL;DR: The emergence of new drugs for mCRPC has improved treatment options dramatically and the best strategies for patient selection and optimal sequential use to achieve the longest cumulative survival improvement and to prevent early resistance remain unclear.
References
More filters
Journal ArticleDOI
The Sequence Alignment/Map format and SAMtools
Heng Li,Bob Handsaker,Alec Wysoker,T. J. Fennell,Jue Ruan,Nils Homer,Gabor T. Marth,Gonçalo R. Abecasis,Richard Durbin +8 more
TL;DR: SAMtools as discussed by the authors implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments.
Journal ArticleDOI
Fast gapped-read alignment with Bowtie 2
TL;DR: Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
Journal ArticleDOI
Cutadapt removes adapter sequences from high-throughput sequencing reads
TL;DR: The command-line tool cutadapt is developed, which supports 454, Illumina and SOLiD (color space) data, offers two adapter trimming algorithms, and has other useful features.
Journal ArticleDOI
BEDTools: a flexible suite of utilities for comparing genomic features
Aaron R. Quinlan,Ira M. Hall +1 more
TL;DR: A new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format, which allows the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks.
Journal ArticleDOI
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
TL;DR: The ANNOVAR tool to annotate single nucleotide variants and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP is developed.
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