Targeting of DNA damage repair /replicative stress pathways with systemic therapies such as poly(ADP-ribose) polymerase (PARP) inhibitors or checkpoint kinase 1 (CHEK1/CHK1) inhibitors or cell cycle pathways with CDK inhibitors have yet to be as established in PanNETs as in other cancers, but our findings suggest a potentially targetable subset of PanNET patients with DNA replicative stress pathway alterations and poor prognosis that are primarily driven by RB1 and TP53 [11–13]. Here, TP53 is linked to cancer.