Fig. 4: CXCR blockade can reverse ARSI resistance in patients with mCRPC.

a, Treatment duration of response-evaluable patients grouped by AZD5069 dose (n = 21). Blue, patient classed as a partial responder; green, patient classed as a non-responder. Legend and coloured tiles indicate previous ARSI: enzalutamide (yellow), abiraterone (brown), apalutamide (dark green); AR-V7 protein status: nuclear Histo-score (HS) ≥ 10 (brown), nuclear HS < 10 (blue); PTEN protein status: nuclear or cytoplasmic HS ≥ 10 (brown), nuclear and cytoplasmic HS < 10 (blue), not available (grey); TP53, AR and PTEN–PI3K pathway genes, and CDKN1B genomic aberration status: no detectable alteration (green), pathogenic mutation (magenta), amplification (purple) and deletion (black) in baseline biopsies or cell-free DNA. b, Best PSA responses (n = 20). One patient was not evaluable for PSA response owing to early clinical disease progression. c, Best radiologic response in patients with measurable disease (n = 13). d,e, Example computerized tomography scan images of measurable disease taken pre-treatment and on treatment in two patients classed as partial responders treated at AZD5069 160 mg BD (d) and AZD5069 120 mg BD (e). White bars in d demarcate the short axis of a lymph node metastasis. f,g, Boxplots of mean blood neutrophil counts on treatment (f) and cycle 2 day 1 (C2D1) neutrophil counts (g) in patients classed as partial responders (n = 5) versus those classed as non-responders (n = 16). In f,g, data are presented individually and as boxplots in which the middle horizontal line is the median, the lower and upper hinges are the first and third quartiles, and the whisker extends from the hinge to the largest and smallest values no further than 1.5 × interquartile range (IQR) from the hinge. Two-sided Mann–Whitney U-test P values are shown. h,i, Expression of AR activity (h) and AR-V7 mRNA signatures (i) in same-patient pre- and on-treatment tumour biopsies (n = 7 pairs) with myeloid count decrease. In h,i, data are presented individually and as boxplots for which the middle line is the median, the lower and upper hinges are the first and third quartiles, and the upper and lower whiskers extend from the hinge to the maximum and minimum values. Grey lines link same-patient, paired samples. Two-sided paired Wilcoxon signed-rank test P values are shown.