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Figure 4. The role of PAK4 in cell signaling: external signals initiate the activation of small GTPases Cdc42 and Rac, which in turn bind
to and activate PAK4. PAK4 has roles in cytoskeletal organization, motility, adhesion, and the regulation of gene expression. mRNA and
protein levels of PAK4 are often seen to be overexpressed in several types of cancer, such as breast cancer and pancreatic cancer. GBD:
GTPase binding domain

CONCLUSION
This review has highlighted some of the RTK regulated pathways that are important for cancer and for
drug development. Several important RTK regulated pathways have been discussed. It is important to
remember, however, that there is are many more RTKs than we have discussed here. In fact there are at
least 58 unique RTKs, which fall into at least 20 families [123] . Several different drugs have been developed
against proteins that are improperly regulated in RTK pathways. Even more are currently in development
or under clinical trials. Some of these have had promising outcomes. It is important to remember, however,
that serious challenges remain ahead. One issue is the development of resistance to drugs that were initially
[2]
successful . To address this, current and future studies need to address the reason for this resistance,
and the development of new drugs that will be effective for resistant cancers [124] . Another challenge is
the development of combination treatments. Single agent treatments are often not sufficient for effective
treatments, but drug combinations can be more effective. One promising area of study is the combination
of protein kinases with immune complex inhibitors, in order to combine immunomodulation with
inhibition of RTK signaling pathways. Finally, identifying which treatments will be most effective in each