Targeting CXCR1 and CXCR2 to overcome radiotherapy resistance in PTEN-deficient prostate carcinoma

Functional impairment of the tumor suppressor PTEN is common in primary prostate cancer and has been linked to relapse post-radiotherapy (RT). Pre-clinical modelling supports elevated CXC-chemokine signaling as a critical mediator of PTEN-depleted disease progression and therapeutic resistance. Our objective was to assess the correlation of PTEN-deficiency with CXC-chemokine signaling and its association with clinical outcomes. Gene expression analysis characterized a PTENLOW/CXCR1HIGH/CXCR2HIGH cluster of tumors that associates with earlier time-to-biochemical recurrence (HR 5.87, p