Description:
- Treatment and prevention of tumor formation and metastasis
- Research reagent (monoclonal antibody)
Abstract
USC scientists recently developed a monoclonal antibody, called 1G6-D7, which targets tumor-secreted Hsp90a. 1G6-D7 binds the active site of tumor-secreted Hsp90a and inhibits both de novo tumor formation and expansion of pre-formed tumors in mice. This development suggests an alternative therapeutic approach to target Hsp90 in cancer, i.e. selective inhibition of the tumour-secreted Hsp90a, instead of the intracellular Hsp90a and Hsp90b that have been proven toxic.
Benefit
- An alternative therapeutic approach to target Hsp90 in cancer by targeting tumor-secreted Hsp90a
- 1G6-D7 Mab shown to inhibit new tumor formation, growth of existing tumors, and metastasis in mouse CDX models
- Potential to treat multiple types of cancer, including but not limited to breast and lung cancer
Market Application
Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (a and b) have been shown to support tumor progression. Targeting intracellular Hsp90, however, has proven too toxic to cancer patients resulting in a very small number of trials advancing to receive regulatory approval for human treatment to date.
The role of extracellular Hsp90 in cancer recently has been unveiled by USC scientists who showed that secreted Hsp90a is essential for tumor formation, invasion, and metastasis of triple negative breast cancer. In contrast to normal cells, which do not secrete Hsp90-a under physiological conditions, more than 50% of all invasive, HIF-1-positive tumors in humans constitutively secrete Hsp90-a. Furthermore, targeting the secreted form of Hsp90 does not affect normal tissue functions. Therefore, selective inhibition of tumor-secreted Hsp90a, which is nonessential for normal cells, could be an effective therapeutic approach for certain cancers.
Publications
Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression. Oncogene. (2016).
Other
- Tested in vitro and in vivo (CDX model)