The rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase (MEK)/ERK, PI3K/mTOR/AKT, Ral guanine nucleotide exchange factor/Ral, and T cell lymphoma invasion and metastasis 1/Rac initiated by HRAS-mediated signaling pathways have divergent and critical roles in tumor progression and evolution through crosstalk and feedback interactions between tumor cell–tumor cell or tumor cell–TME [78, 79]. The gene discussed is RALGDS; the disease is fibrosarcoma.