Conclusions

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

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The last several years have seen an increase in the number of targeted antimitotic drug discovery efforts as proteins critical for kinetocore, centrosome, and mitotic spindle function continue to be elucidated. The rapid progress made in progressing mitotic kinesin inhibitors into proof of concept clinical trials serves as a benchmark for the potential of this realm of anticancer drug discovery. The KSP inhibitor, ispinesib, has been studied in Phase II clinical trials against locally advanced or metastatic breast cancer (in which it has demonstrated anti-cancer activity), platinum-refractory and -sensitive non-small cell lung cancer, ovarian cancer, he-patocellular cancer, colorectal cancer, head and neck cancer, hormone-refractory prostate cancer, and melanoma. A second KSP inhibitor, SB-743921, has entered Phase I studies. In addition, a number of other potent and structurally diverse structures are in pre-clinical development, most if not all of which bind to the same induced-fit, allosteric pocket as monastrol. With another 13 proteins designated as mitotic kinesins, efforts against this target class are still at an early stage. Continued clinical development of KSP targeting agents should serve to bolster the interrogation of these unique proteins as anticancer targets.

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