Here, we presented two different methods of PKA and ERK modulation that have the potential to suppress cancer progression and metastasis-related lethality while being cardio-safe or even protective against heart disease: (i) Treatment with partial RKIP “mimics”, such as low-dose drug combinations that target the stress MAPK network, could potentially suppress metastasis in tumors while enabling beneficial Raf/MEK/ERK1/2 and βAR/PKA signaling in cardiac cells. The gene discussed is MAPK1; the disease is cancer.