The HMGB1-CXCL12 complex can induce a range of downstream aggressive behaviors, including: (1) gemcitabine treatment resistance [60]; (2) promoting proliferation, EMT, angiogenesis and metastasis of PDA cells [61]; (3) elevating MMP2,9 expression, cancer cells invasion and migration [60–62]; (4) activating other pathways, such as PI3K/Akt signaling, Ras/ERK pathway [63]; and (5) blunting immunotherapeutic efficacy, inducing immunosuppressive status [64]. Here, AKT1 is linked to Patent ductus arteriosus.