This reflects, predominantly, the regulatory role of AKT in DNA double-stand break (DSB) repair, including non-homology end-joining (NHEJ) and homologous recombination (HR)—mediated DNA repair, which in turn also illustrates the AKT-mediated pathway, a perspective target to sensitize STS and GIST to DNA-damaging agents, including topoisomerase II (Topo II) inhibitors. The gene discussed is AKT1; the disease is telomere syndrome.