A function for the lck proto-oncogene

This chapter provides a general survey of validated and emerging molecular targets for cancer drug discovery and development, with a focus on those explored for the discovery of molecularly targeted cancer therapeutics. The targeting of oncogenic protein tyrosine kinase signal transduction pathways in cancer cells ushered in the molecularly targeted approach to therapeutics. The signaling cascade is initiated by the growth factors binding to their cognate receptor tyrosine kinases (RTKs) at the extracellular domain. Protein and lipid kinases modulate the cellular functions of numerous other proteins and play critical roles in signal transduction pathways of cell growth and proliferation. The chapter explains the major receptor and cytosolic tyrosine kinases identified as novel cancer targets. It is found that, in addition to the HER or erbB family of oncogenic RTKs, several other RTKs constitute potential novel molecular targets for cancer drug discovery such as the platelet-derived growth factor receptor. The transcription factor hypoxia-inducible factor has also been shown to be important in cancer progression and angiogenesis. Its overexpression has been correlated with treatment failure and mortality in brain, breast, cervical, esophageal, oropharyngeal, and ovarian cancers.