Identification of targets in tumor cells vs normal cells (or at least a differential in their expression) is certainly a promising method for approaching the treatment and, indeed, the prevention of cancer. Presently, targeting of patient tumor cells has taken on even greater importance and interest with the discovery of the new agent imatinib(Drug information on imatinib) mesylate (STI571, Gleevec), which is targeted to a kinase present in chronic myeloid leukemia (CML) cells (p210 BCR-ABL abnormal cells), which is required for CML cells to survive, but is not present in normal leucocytes. The results with this agent targeted to the p210 BCR-ABL tyrosine kinase are indeed spectacular. The agent is of even greater interest in that it also works against some gastrointestinal stromal sarcomas with gain of function mutations in c-kit (CD117). This activity of a targeted agent against a solid tumor increases the interest in targeted therapy to an even greater degree.
Of course, there are multiple other examples of targeted (or semi-targeted) therapies, such as monoclonal antibodies (to CD20, CD33, CD52 or HER2/neu), aromatase inhibitors, antiestrogens, and many others.
Even agents such as inhibitors of topoisomerase I hit a target that is present to a greater degree in tumor cells than in normal cells. More specific targeting should give us significant new therapeutic and preventive agents.
This special issue of ONCOLOGY is devoted to a series of papers presented in part at an educational satellite symposium held in conjunction with the American Society of Clinical Oncology 2001 Annual Meeting. The symposium was convened to specifically examine vascular endothelial growth factor (VEGF) and cyclooxygenase (COX)-2 as potential new targets in cancer treatment and prevention. The presentations were outstanding, but I think the reader will find these papers of even more interest.
More specifically, Drs. Anzick and Trent of the Cancer Genetics Branch of the National Human Genome Research Institute, National Institutes of Health, give us an outstanding overview of the role of genomics in identifying new targets for cancer therapies. This extremely well-written article clearly presents the potential for the use of genomics in the day-to-day care of the patient with cancer. In the article, they delineate the use of:
- complementary DNA microarray to improve tumor classification and to provide potential new targets (and clues as to the location of those targets in pathways critical to cell survival);
- tissue arrays to determine how frequently a particular target is found in a particular tumor type and to determine the clinical significance of that particular target; and
- single-nucleotide polymorphism analysis to predict either toxicity or response, or both, to a particular drug.
An overview of the role of angiogenesis in oncology, including inhibitors of angiogenesis, is provided by Dr. Lee Ellis and colleagues of The University of Texas M. D. Anderson Cancer Center. They give an outstanding review of VEGF as a target associated with an aggressive phenotype in numerous solid malignancies. They also discuss the angiopoietins, COX-2, and numerous nonspecific angiogenic factors. The tables and figures in this article give us an idea of the possible redundancy in the process of angiogenesis and the challenges in targeting tumor angiogenesis.
Dr. Francis Giles of M. D. Anderson Cancer Center teaches us about the importance of increased angiogenesis in the pathogenesis of hematologic malignancies. In particular, Dr. Giles emphasizes VEGF as a proangiogenic factor (along with the other possible functions for VEGF in the pathogenesis of hematologic malignancies) and discusses various methods being used to intervene to discover the effects of VEGF.