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This is the final part of a four-part serial review on oncogenes and their potential use as targets for cancer therapy. Previous sections discussed various categories of oncogenes (growth factors, tyrosine kinases, intermediate signaling molecules, and transcription factors) and the advances made in various strategies being used to alter their actions. This part describes four oncogenes, MDM2, BCL2, XIAP, and Survivin, that are involved in regulation of the cell cycle and apoptosis. [ABSTRACT FROM AUTHOR]

This is the third paper in a four-part serial review on potential therapeutic targeting of oncogenes. The previous parts described the involvement of oncogenes in different aspects of cancer growth and development, and considered the new technologies responsible for the advancement of oncogene identification, target validation, and drug design. Because of such advances, new specific and more efficient therapeutic agents can be developed for cancer. This part of the review continues the exploration of various oncogenes that we have grouped within seven categories: growth factors, tyrosine kinases, intermediate signaling molecules, transcription factors, cell cycle regulators, DNA damage repair genes, and genes involved in apoptosis. Part one discussed growth factors and tyrosine kinases and part two discussed intermediate signaling molecules. This portion of the review covers transcription factors and the various strategies being used to inhibit their expression or decrease their activities. [ABSTRACT FROM AUTHOR]

This is the second part of a four-part review on potential therapeutic targeting of oncogenes. The previous part introduced the new technologies responsible for the advancement of oncogene identification, target validation, and drug design. Because of such advances, new specific and more efficient therapeutic agents can be developed for cancer. This part of the review continues the exploration of various oncogenes, which we have grouped within seven categories: growth factors, tyrosine kinases, intermediate signaling molecules, transcription factors, cell cycle regulators, DNA damage repair genes, and genes involved in apoptosis. Part I included a discussion of growth factors and tyrosine kinases. This portion of the review covers intermediate signaling molecules and the various strategies used to inhibit their expression or decrease their activities. [ABSTRACT FROM AUTHOR]

In the past 10 years, progress made in cancer biology, genetics, and biotechnology has led to a major transition in cancer drug design and development. There has been a change from an emphasis on non-specific, cytotoxic agents to specific, molecular-based therapeutics. Mechanism-based therapy is designed to act on cellular and molecular targets that are causally involved in the formation, growth, and progression of human cancers. These agents, which may have greater selectivity for cancer versus normal cells, and which may produce better anti-tumor efficacy and lower host toxicity, can be small molecules, natural or engineered peptides, proteins, antibodies, or synthetic nucleic acids (e.g. antisense oligonucleotides, ribozymes, and siRNAs). Novel targets are identified and validated by state-of-the-art approaches, including high-throughput screening, combinatorial chemistry, and gene expression arrays, which increase the speed and efficiency of drug discovery and development. Examples of oncogene-based, molecular therapeutics that show promising clinical activity include trastuzumab (Herceptin®), imatinib (Gleevec®), and gefitinib (Iressa®). However, the full potential of oncogenes as novel targets for cancer therapy has not been realized and many challenges remain, from the validation of novel targets, to the design of specific agents, to the evaluation of these agents in both preclinical and clinical settings. In maximizing the benefits of molecular therapeutics in monotherapy or combination therapy of cancer, it is necessary to have an understanding of the underlying molecular abnormalities and mechanisms involved. This is the first part of a four-part review in which we discuss progress made in the last decade as it relates to the discovery of novel oncogenes and signal transduction pathways, in the context of their potential as targets for cancer therapy. This part delineates the latest discoveries about the potential use of growth factors and protein tyrosine kinases as targets for therapy. Later parts focus on intermediate signaling pathways, transcription factors, and proteins involved in cell cycle, DNA damage, and apoptotic pathways. [ABSTRACT FROM AUTHOR]