Challenges and opportunities in defining the essential cancer kinome.

Signaling pathways controlled by protein kinases underlie a large fraction of human diseases and participate in the development and progression of all forms of cancer. Targeted therapeutic strategies to treat cancer and other diseases are focused almost exclusively on protein kinases, with a strong bias toward a small subset of the entire human kinome. RNA interference (RNAi)-based screens for protein kinase requirements have revealed a surprisingly high degree of diversity between cancer cell lines in their dependence on specific protein kinases. These screens also demonstrate that some of the most critical protein kinases for the proliferation and survival of cancer cell lines are also the least studied. Although the concept of oncogene addiction is powerful in designing therapeutic strategies to treat cancer, unbiased kinome-specific and genome-wide RNAi screens are revealing unexploited areas of potential therapeutic intervention.