Editorial [ Purine Binding Proteins as Anti-Cancer Targets Guest Editor: Dr. Zhenhai Gao ]

The explosion of genomic information has led to the identification of a plethora of genes that are responsible for the malignant phenotypes of human cancers. Over the past two decades, the new paradigm and strategy in cancer therapy has been to develop agents that specifically target key molecules and signaling pathways involved in tumor growth and progression. The molecularly targeted therapy is widely expected to hold the potential of providing a much improved risk/benefit ratio, compared with conventional cytotoxic chemotherapy. A prominent class of such targets, perhaps one of the most abundant target sources for oncology drug discovery, is the protein kinase family. ATP binding kinases play pivotal roles in oncogenic signal transduction. Indeed, the recent approval of several kinase inhibitors including Gleevec, Iressa, Tarceva, Nexavar and Sutent has firmly established the eminent drugability of protein kinases. We know now that the human genome might encode as many as 518 protein kinases, and about 20-30% of pharmaceutical discovery programs are currently focused on various kinases. However, kinases are only part of a larger family of purine binding proteins in human genome, collectively called "purinome". Structural analysis has indicated that the non-kinase purine binding proteins bind purines in a similar orientation as observed in kinases. Therefore, the utility of purinome as drug targets can be expanded beyond kinases to include many non-kinase purine binding proteins. Undoubtedly, this will further increase the diversity and broaden our repertoire of drugable targets. In fact, several non-kinase purine binding proteins, e.g. heat shock protein 90 (hsp90), Eg-5, and small G protein Rac, have recently emerged as very promising and attractive anti-cancer targets. This special issue of "Current Topics in Medicinal Chemistry" is devoted to the review and highlight of the most recent achievements in pre-clinical and clinical development of small molecule drugs targeting purine binding proteins in cancer. The excellent papers from five research groups will cover the unique aspects of different classes of purine utilizing enzymes as drug targets, including Raf-1 (kinase), Hsp90 (ATPase) and Rac (GTPase), as well as discuss the state-of-art approaches such as structure based drug design (SBDD) and chemoproteomic technology (proteome mining) that are currently being explored in purine binding protein based drug discovery. It is my hope that these comprehensive and stimulating review articles will be beneficial to many scientists who are actively engaged in this very promising and exciting area of drug development research. I would like to express my gratitude to Dr. Allen B. Reitz for inviting me to be the Guest Editor for this special issue. I am also very thankful to the following colleagues who have served as the reviewers of this issue: Drs. David Duhl, Paul Renhowe, Timothy Machajewski and Guoying (Karen) Yu. Finally, I would like to offer my special thanks to all authors for their enthusiasm and dedication, which have made this special issue a reality.