PIK3CA and substance dependence: We observed a similar correlation pattern in the network and enrichment analysis on the STRING software 12.0, where BRAF, MEK, and PI3K showed varying degrees of interactions with other genes, such as KSR1 and KSR2, which activate Raf/MEK/ERK pro-tumorigenic signaling in RAS-dependent cancers [44,45]; RALGDS, a mediator of KRAS oncogenic signaling [46]; and MAP2K2, which instigates the MAPK/ERK pathway upregulated in tumors more than normal tissue in colorectal cancer studies [47,48] (Figure 7D).