Survival: Kinase pathways regulate programmed cell death by either directly modulating apoptosis regulators or altering their expression. Necroptosis is controlled by signaling pathways that intersect apoptosis regulators, including RIPK3. Motility: Cytoskeletal dynamics are mediated by RTKs and integrin clustering to promote the activation of FAK and GTPases. Effector kinases include ROCK1, MLCK (encoded by MYLK3), PAK1, and LIMK1. Evading antitumor immunity: Numerous cell types, including CTLs, Tregs, DCs, MDSCs, and macrophages, are actively involved in modulating the tumor immune response. MAP4K1, PI3K∂, MST1R, MERTK, and PKCη, represent potential targets for reversing the myriad mechanisms involved in tumor-mediated immunosuppression of the tumor microenvironment. Proliferation: MAPK pathway components increase levels of CCND1. CCND1 regulates the activity of CDK4/6 and, in turn, induces cell cycle progression via RB1 and E2F transcriptional regulators. DNA damage checkpoints: Following induction of double-strand DNA breaks by ionizing radiation or chemotherapeutic agents, ATM and ATR phosphorylate CHK1. Activated CHK1 subsequently prevents cell cycle progression and induces DNA repair mechanisms. Angiogenesis: Tumor cells modulate the microenvironment by secreting angiogenic factors (ligands for VEGFR, FGFRs, and the angiopoietin receptor TIE2 [encoded by TEK]) to stimulate endothelial cells and enhance vascularization. Pericytes are in turn stimulated by PDGF and TGF growth factors to contribute to endothelial cell proliferation and migration. Metabolism: PI3K/AKT pathway activity is directly correlated with increased glucose metabolism in cancer cells. Signaling is mediated through hexokinases, MTOR, and HIF1α (encoded by HIF1A) to increase oxidative phosphorylation, tricarboxylic acid cycle, and mitochondrial respiration.