Signaling network response to alpha-particle targeted therapy with actinium-225 labeled minigastrin analogue 225Ac-PP-F11N

Alpha-particle emitters have recently been explored as valuable therapeutic radionuclides. Yet, toxicity to healthy organs and cancer radioresistance limit the efficacy of targeted alpha-particle therapy (TAT). Identification of the radiation-activated mechanisms, which drive cancer cell survival, provides opportunities to develop new points for therapeutic interference to improve the efficacy and safety of TAT. Quantitative phosphoproteomics and matching proteomics followed were employed to identify alterations in the signaling networks in response to TAT with actinium-225 labeled minigastrin analogue 225Ac-PP-F11N in A431 cells, which overexpress cholecystokinin B receptor (CCKBR).