American Journal of Pharmacogenomics

, Volume 5, Issue 3, pp 173–190 | Cite as

Oncogenes as Novel Targets for Cancer Therapy (Part I)

Growth Factors and Protein Tyrosine Kinases
  • Zhuo Zhang
  • Mao Li
  • Elizabeth R. Rayburn
  • Donald L. Hill
  • Ruiwen Zhang
  • Hui WangEmail author
Targeted Therapeutics


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.


Vascular Endothelial Growth Factor Tyrosine Kinase Imatinib Trastuzumab Hepatocyte Growth Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This project was supported by grants from the National Institutes of Health/National Cancer Institute (R01 CA 80698 and R01 CA112029). Dr Wang was supported in part by funds from the Comprehensive Cancer Center, University of Alabama at Birmingham. Dr Z. Zhang was supported in part by a post-doctoral fellowship from the Department of Defense Prostate Cancer Research Program (grant number W81XWH-04-1-0845).

We realize that, due to the limitation of space, we could not cite all the excellent contributions published in this field, and we apologize for omission of many papers and reviews from our national and international colleagues.

The authors have no potential conflicts of interest that are directly relevant to the content of this review.


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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Zhuo Zhang
    • 1
  • Mao Li
    • 1
  • Elizabeth R. Rayburn
    • 1
  • Donald L. Hill
    • 1
    • 2
  • Ruiwen Zhang
    • 1
    • 2
    • 3
  • Hui Wang
    • 1
    • 2
    Email author
  1. 1.Department of Pharmacology and Toxicology, and Division of Clinical PharmacologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Comprehensive Cancer CenterUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Gene Therapy CenterUniversity of Alabama at BirminghamBirminghamUSA

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