Engineering enzymatically activated "molecular grenades" for cancer |
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Authors: | Samuel R Denmeade John T Isaacs |
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Affiliation: | The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore MD. |
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Abstract: | Animal toxicology and clinical phase I trial data have documented that the PSMA-activated thapsigargin drug, G202 is non-myelosuppressive. This lack of myelosuppression facilitates G202 combination with a variety of additional clinically approved drugs. For example, thapsigargin's ability to induce ER stress raises its potential for synergy when combined with radiation and cytotoxic chemotherapies. Finally, G202-based delivery of the thapsigargin analog causes marked reduction of expression of the androgen receptor (AR) in prostate cancer cells and the estrogen receptor (ER) protein in breast cancer. These results suggest that combination therapy with anti-androgen/estrogens and G202 could be synergistic against prostate and/or breast cancer. These combinatorial approaches are currently under pre-clinical evaluation in our laboratories. |
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