Secondary messengers such as cAMP and calcium can also play a role in GEF activation. Crosstalk has also been shown between GEFs and multiple GTPase signaling pathways. For example, SOS contains a Dbl homology domain in addition to its CDC25 catalytic domain. SOS can act as a GEF to activate Rac1, a RhoGTPase, in addition to its role as a GEF for Ras. SOS is therefore a link between the Ras-Family and Rho-Family GTPase signaling pathways. GEFs are potential target for cancer therapy due to their role in many signaling pathways, particularly cell proliferation. For example, many cancers are caused by mutations in the MAPK/ERK pathway that lead to uncontrolled growth. The GEF SOS1 activates Ras, whose target is the kinase Raf. Raf is a proto-oncogene because mutations in this protein have been found in many cancers. The Rho GTPase Vav1, which can be activated by the GEF receptor, has been shown to promote tumor proliferation in pancreatic cancer. GEFs represent possible therapeutic targets as they can potentially play a role in regulating these pathways through their activation of GTPases.