Conclusions

Although the overall mechanism of action of topoisomerase inhibitors is well understood, there are yet few molecular-level details of the critical enzyme-drug-DNA ternary complexes that are formed. It is thus difficult to apply modern structural biology tools to the design of better agents. Nevertheless, this review shows that there is a vigorous research program into the development of new topoisomerase agents. This takes two general approaches. In the absence of detailed structural biology, a...

Disclaimer Not for patient use To be used as a research guide only

(monitors and predictors of disease risk, progression, improvement, and severity) surrogate endpoints (substitutes or correlates with measurable clinical endpoints such as how a patient feels, functions, or survives, e.g., viral titer, serum cholesterol, blood pressure) pharmacogenomic biomarker (monitors or predicts drug response, e.g., Her2 neu, EGFR single nucleotide polymorphisms (SNPs), CYP2D6 variants) pharmacodynamic biomarkers (demonstrates that a drug is on target and correlates with...

Review Revicell White

Rosenberg, S. A. Cancer Principles and Practice of Oncology Lippincott-Raven Philadelphia, PA, 1997. 2. American Cancer Society. Cancer Facts and Figures. www.cancer.org (accessed Aug 2006). 3. Hanahan, D. Weinberg, R. A. Cell 2000, 100, 57-70. 4. Vogelstein, B. Kinzler, K. W Nat. Med. 2004, 10, 789-799. 5. Fearon, E. R. Vogelstein, B. Cell 1990, 61, 759-767. 6. Vogelstein, B. Fearon, E. R. Hamilton, S. R. Kern, S. E. Preisinger, A. C. Leppert, M. et al. N. Engl. J....

Signal Transduction and Cancer

What Neoplasia Tree Model Flow Chart

Cancer is a complex family of diseases characterized by host of cells that have acquired a malignant phenotype, rendering them more genetically unstable and less responsive to external stimuli and their own environment. In a landmark paper, Hanahan and Weinberg have described six 'hallmarks of cancer' that collectively lead to malignant growth5 self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis,...

References

National Breast Cancer Foundation Inc. and symptoms index.html accessed April 2006 . 2. Beatson, G. Lancet 1896, 2, 104-107. 3. Holtkamp, D. E. Greslin, S. C. Root, C. A. Lerner, L. J. Proc. Soc. Exp. Biol. Med. 1960, 105, 197-201. 4. Huppert, L. C. Fertil. Steril. 1979, 31, 1. 5. Beall, P T. Misra, L. K. Yound, R. L. Spjut, H. J. Evans, H. J. Leblanc, A. Calcif. Tissue Int. 1984, 36, 123-127. 6. Chakraborty, P K. Brown, J. L. Ruff, C. B. Nelson, M. F Mitchell, A. S. J. SteroidBiochem. Mol....

Bn80927

BN-80927 29 is a homocamptothecin and a potent topo I poison, but also a catalytic inhibitor of topo II.154,155 It has excellent cytotoxicity against a number of human tumor cell lines in culture e.g., IC50 of 6.6 and 3 nM in HT29 colon and DU-145 prostate cell lines respectively .156 BN-80927 was more potent than SN38 6 in both wild-type and camptothecin-resistant tumor cell lines, and was highly effective in tumor xenografts of the human androgen-independent prostate tumors PC-3 and DU-145...

Erx

The clinical effectiveness of the taxanes has paved the way for the more recently discovered nontaxane microtubule-stabilizing agents. These new compounds, most discovered in the last 10 years, have provided new avenues for research in cancer chemotherapy, as well as significant challenges to the synthetic community to supply sufficient quantities of these frequently complex structures. The early clinical success of the epothilones is an encouraging first step toward the introduction of a...