In line with this notion, mutations in PCa that activate PI3K (such as prostate-specific Pten loss) prime or promote obesity-driven PCa aggressiveness in conjunction with other signalling pathways, such as loss of Ptpn1 [221], IL6/pSTAT3 signalling activation [222] or Pml co-deletion [223]. Here, IL6 is linked to obesity due to melanocortin 4 receptor deficiency.