title: TMPRSS2-ERG in Blood and Docetaxel Resistance in Metastatic Castration-resistant Prostate Cancer.
abstract: TMPRSS2-ERG rearrangement is a genetic alteration exclusive to prostate cancer, associated with taxane resistance in preclinical models. Its detection in blood samples of metastatic resistant prostate cancer (mCRPC) patients may indicate the presence of circulating tumour cells with this genetic alteration and may predict taxane resistance. To test this hypothesis, we evaluated TMPRSS2-ERG expression using quantitative reverse transcription polymerase chain reaction in peripheral blood mononuclear cells and tumour tissue from mCPRC patients treated with taxanes. We examined peripheral blood mononuclear cells from 24 healthy controls, 50 patients treated with docetaxel, and 22 with cabazitaxel. TMPRSS2-ERG was detected in 0%, 16%, and 22.7% of them, respectively. In docetaxel-treated patients TMPRSS2-ERG detection correlated with lower prostatic-specific antigen (PSA) response rate (12.5% vs 68.3%, p=0.005), PSA-progression-free survival (PFS; 3.1 mo vs 7.5 mo, p<0.001), clinical/radiological-PFS (3.1 mo vs 8.2 mo, p<0.001), and it was independently associated with PSA-PFS (hazard ratio 3.7; p=0.009) and clinical/radiological-PFS (hazard ratio 6.3; p<0.001). Moreover, TMPRSS2-ERG also predicted low PSA-PFS to cabazitaxel. At progression, a switch from negative to positive TMPRSS2-ERG was observed in 41% of patients with undetected TMPRSS2-ERG at the baseline sample. Tissue TMPRSS2-ERG expression correlated with lower PSA-PFS (p=0.02) to docetaxel. Our findings support the potential role of TMPRSS2-ERG detection as a biomarker to tailor treatment strategies.
  
  
  
  Taxanes are the most active chemotherapy agents in metastatic resistant prostate cancer. However, not all patients respond to this therapy. In the present study we show that the detection of TMPRSS2-ERG in blood from metastatic resistant prostate cancer patients predicts resistance to docetaxel and it may be useful to select treatment and to avoid possible toxicities in refractory patients.
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Òscar
authors.initials: Ò
authors.lastname: Reig
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Marín-Aguilera
authors.affiliation: Medical Oncology Department, Hospital Plató, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Carrera
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Jiménez
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Paré
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: García-Recio
authors.affiliation: Medical Oncology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Gaba
authors.affiliation: Medical Oncology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: Maria Verónica
authors.initials: MV
authors.lastname: Pereira
authors.affiliation: Department of Pathology, Hospital Clínic, Barcelona, Spain; University of Barcelona, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Fernández
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain; University of Barcelona, Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumours Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Barcelona, Spain. Electronic address: bmellado@clinic.ub.es.
authors.forename: Begoña
authors.initials: B
authors.lastname: Mellado
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000235:genetics; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011467:Prostate / Q000000981:diagnostic imaging / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D043823:Taxoids; D000077143:Docetaxel; C552428:cabazitaxel; D017430:Prostate-Specific Antigen
keywords: Biomarker; Docetaxel; Prostate cancer; Resistance; TMPRSS2-ERG