Their role is underscored by the accumulation of mutations in additional regulators of their activation during the course of this tumor's treatment: MAPK (SPRY3) (Cabrita and Christofori 2008), PI3K (DEPDC5) (Cabrita and Christofori 2008; Bar-Peled et al. 2013), and WNT (KREMEN2, NET1, GPR124) (Orlow et al. 1987; Mao et al. 2002; Posokhova et al. 2015; Wei et al. 2017). The gene discussed is SPRY3; the disease is neoplasm.