Abstract
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor produced by tumor cells under hypoxic conditions, and a key regulator of a number of genes important in cancer biology. Over-expression of HIF-1α in human tumors is associated with poor prognosis and poor therapeutic outcomes and HIF-1α has been suggested as a novel target for cancer therapy. This article provides a review of PX-478 as the first novel HIF-1α inhibitor in clinical stage for the treatment of solid tumors.
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Aebersold, D. M., Burri, P., Beer, K. T., Laissue, J., Djonov, V., Greiner, R. H., and Semenza, G. L., Expression of hypoxiainducible factor-1α: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res., 61, 2911–2916 (2001).
Belozerov, V. E. and Van Meir, E. G., Hypoxia inducible factor-1: a novel target for cancer therapy. Anticancer Drugs, 16, 901–909 (2005).
Koh, M. Y., Spivak-Kroizman, T., Venturini, S., Welsh, S., Williams, R. R., Kirkpatrick, D. L., and Powis, G., Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha. Mol. Cancer Ther., 7, 90–100 (2008).
Kung, A. L., Wang, S., Klco, J. M., Kaelin, W. G., and Livingston, D. M., Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat. Med., 6, 1335–1340 (2000).
Lee, J. W., Bae, S. H., Jeong, J. W., Kim, S. H., and Kim, K. W., Hypoxia-inducible factor (HIF-1)α: its protein stability and biological functions. Exp. Mol. Med., 36, 1–12 (2004).
Macpherson, G. R. and Figg, W. D., Small molecule-mediated anti-cancer therapy via hypoxia-inducible factor-1 blockade. Cancer Biol. Ther., 3, 503–504 (2004).
Onnis, B., Rapisarda, A., and Melillo, G., Development of HIF-1 inhibitors for cancer therapy. J. Cell. Mol. Med., 13, 2780–2786 (2009).
Schwartz, D. L., Powis, G., Thitai-Kumar, A., He, Y., Bankson, J., Williams, R., Lemos, R., Oh, J., Volgin, A., Soghomonyan, S., Nishii, R., Alauddin, M., Mukhopadhay, U., Peng, Z., Bornmann, W., and Gelovani, J., The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol. Cancer Ther., 8, 947–958 (2009).
Schwartz, D. L., Bankson, J. A., Lemos, R., Jr., Lai, S. Y., Thittai, A. K., He, Y., Hostetter, G., Demeure, M. J., Von Hoff, D. D., and Powis, G., Radiosensitization and stromal imaging response correlates for the HIF-1 inhibitor PX-478 given with or without chemotherapy in pancreatic cancer. Mol. Cancer Ther., 9, 2057–2067 (2010).
Tibes, R., Falchook, G. S., Von Hoff, D. D., Weiss, G. J., Iyengar, T., Kurzrock, R., Pestano, L., Lowe, A. M., and Herbst, R. S., Results from a phase I, dose-escalation study of PX-478, an orally available inhibitor of HIF-1α. J. Clin. Oncol., 28, abstr 3076 (2010).
Welsh, S., Williams, R., Kirkpatrick, L., Paine-Murrieta, G., and Powis, G., Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha. Mol. Cancer Ther., 3, 233–244 (2004).
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Edited by Sang-Bae Han, College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea Tel: 82-43-261-2815 E-mail: shan@chungbuk.ac.kr
Hwan Mook Kim College of Pharmacy, Gachon University of Medicine and Science
Main Research Area
Cancer therapeutics: HIF-1, Runx-3, PRX, HDAC
Lead optimization: efficacy, PK, toxicity
Development of new methods of pharmacology
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Lee, K., Kim, H.M. A novel approach to cancer therapy using PX-478 as a HIF-1α inhibitor. Arch. Pharm. Res. 34, 1583–1585 (2011). https://doi.org/10.1007/s12272-011-1021-3
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DOI: https://doi.org/10.1007/s12272-011-1021-3