Reference #: 2003-039
The central problem in clinical management of prostate cancer is the development of hormone-refractory and metastatic disease. Androgen deprivation therapy only provides a temporary inhibition of the cancer growth before the hormone-refractory form of prostate cancer develops. Moreover, no effective pharmacologic treatments exist for elimination of residual cancer cells after prostate cancer surgery. The present invention identifies a new therapeutic target, namely, Signal Transducer and Activator of Transcription (Stat5a/b) that has potential for developing better therapeutic interventions for primary and advanced prostate cancer. It also describes various STAT5 inhibitors and an assay for diagnosing prostate cancer due to activated STAT5 in tissue samples.
- Therapeutic: Inhibition of prostate cancer growth by inhibiting STAT5
- Diagnostic: Assay to identify patients which are at a greater risk of progression of prostate cancer
- Efficient therapy to treat hormone resistant tumor
- Selective inhibition of prostate cancer cells
- Provides a specific drug target against an extremely difficult-to-treat cancer
- Extensive cancerous cell death upon administration
Stage of Development
Proof of principle demonstrated in prostate tumors in vivo.
Tan, S. H., Dagvadorj, A., Shen, F., Gu, L., Liao, Z., Abdulghani, J., Zhang, Y., Gelmann, E. P., Zellweger, T., Culig, Z., Visakorpi, T., Bubendorf, L., Kirken, R. A., Karras, J., and Nevalainen, M. T. Transcription factor Stat5 synergizes with androgen receptor in prostate cancer cells. Cancer Res, 68: 236-248, 2008.
Li, H., Zhang, Y., Glass, A., Zellweger, T., Gehan, E., Bubendorf, L., Gelmann, E. P., and Nevalainen, M. T. Activation of signal transducer and activator of transcription-5 in prostate cancer predicts early recurrence. Clin Cancer Res, 11: 5863-5868, 2005.
Li, H., Ahonen, T. J., Alanen, K., Xie, J., LeBaron, M. J., Pretlow, T. G., Ealley, E. L., Zhang, Y., Nurmi, M., Singh, B., Martikainen, P. M., and Nevalainen, M. T. Activation of signal transducer and activator of transcription 5 in human prostate cancer is associated with high histological grade. Cancer Res, 64: 4774-4782, 2004.
Ahonen, T. J., Xie, J., LeBaron, M. J., Zhu, J., Nurmi, M., Alanen, K., Rui, H., and Nevalainen, M. T. Inhibition of transcription factor Stat5 induces cell death of human prostate cancer cells. J Biol Chem, 278: 27287-27292, 2003.
Methods and compositions for the inhibition of stat5 in prostate cancer cells, USPTO Application# 20070010468
Methods and compositions for the inhibition of STAT5 in prostate cancer cells. PCT PCT/US2004/012799