Stem cell signaling as a target for novel drug discovery: recent progress in the WNT and Hedgehog pathways
Abstract
Songzhu Michael AN1, *, Qiang Peter DING1, Ling-song LI2
1Curegenix Inc, Guangzhou 510663, China; 2Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201203, China
One of the most exciting fields in biomedical research over the past few years is stem cell biology, and therapeutic application of stem cells to replace the diseased or damaged tissues is also an active area in development. Although stem cell therapy has a number of technical challenges and regulatory hurdles to overcome, the use of stem cells as tools in drug discovery supported by mature technologies and established regulatory paths is expected to generate more immediate returns. In particular, the targeting of stem cell signaling pathways is opening up a new avenue for drug discovery. Aberrations in these pathways result in various diseases, including cancer, fibrosis and degenerative diseases. A number of drug targets in stem cell signaling pathways have been identified. Among them, WNT and Hedgehog are two most important signaling pathways, which are the focus of this review. A hedgehog pathway inhibitor, vismodegib (Erivedge), has recently been approved by the US FDA for the treatment of skin cancer, while several drug candidates for the WNT pathway are entering clinical trials. We have discovered that the stem cell signaling pathways respond to traditional Chinese medicines. Substances isolated from herbal medicine may act specifically on components of stem cell signaling pathways with high affinities. As many of these events can be explained through molecular interactions, these phenomena suggest that discovery of stem cell-targeting drugs from natural products may prove to be highly successful.
Keywords: stem cells; signaling pathway; WNT; Hedgehog; cancer; fibrosis; cardiac remodeling; osteoporosis; traditional Chinese medicine; drug discovery
This work was supported by grants from the Chinese Academy of Sciences (XDA01040301) Ministry of Science and Technology of China (2009CB940900, 2010CB944900, 2011CB965104, 2011DFB30010) and the Shanghai Commission of Science and Technology (11DZ2292200).
* To whom correspondence should be addressed.
E-mail man@curegenix.com
Received 2013-02-06 Accepted 2013-04-12
Keywords:
1Curegenix Inc, Guangzhou 510663, China; 2Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201203, China
One of the most exciting fields in biomedical research over the past few years is stem cell biology, and therapeutic application of stem cells to replace the diseased or damaged tissues is also an active area in development. Although stem cell therapy has a number of technical challenges and regulatory hurdles to overcome, the use of stem cells as tools in drug discovery supported by mature technologies and established regulatory paths is expected to generate more immediate returns. In particular, the targeting of stem cell signaling pathways is opening up a new avenue for drug discovery. Aberrations in these pathways result in various diseases, including cancer, fibrosis and degenerative diseases. A number of drug targets in stem cell signaling pathways have been identified. Among them, WNT and Hedgehog are two most important signaling pathways, which are the focus of this review. A hedgehog pathway inhibitor, vismodegib (Erivedge), has recently been approved by the US FDA for the treatment of skin cancer, while several drug candidates for the WNT pathway are entering clinical trials. We have discovered that the stem cell signaling pathways respond to traditional Chinese medicines. Substances isolated from herbal medicine may act specifically on components of stem cell signaling pathways with high affinities. As many of these events can be explained through molecular interactions, these phenomena suggest that discovery of stem cell-targeting drugs from natural products may prove to be highly successful.
Keywords: stem cells; signaling pathway; WNT; Hedgehog; cancer; fibrosis; cardiac remodeling; osteoporosis; traditional Chinese medicine; drug discovery
This work was supported by grants from the Chinese Academy of Sciences (XDA01040301) Ministry of Science and Technology of China (2009CB940900, 2010CB944900, 2011CB965104, 2011DFB30010) and the Shanghai Commission of Science and Technology (11DZ2292200).
* To whom correspondence should be addressed.
E-mail man@curegenix.com
Received 2013-02-06 Accepted 2013-04-12