| First Author | Chugh R | Year | 2012 |
| Journal | Sci Transl Med | Volume | 4 |
| Issue | 156 | Pages | 156ra139 |
| PubMed ID | 23076356 | Mgi Jnum | J:189216 |
| Mgi Id | MGI:5444765 | Doi | 10.1126/scitranslmed.3004334 |
| Citation | Chugh R, et al. (2012) A preclinical evaluation of minnelide as a therapeutic agent against pancreatic cancer. Sci Transl Med 4(156):156ra139 |
| abstractText | Pancreatic cancer is one of the most lethal human malignancies with an all-stage 5-year survival frequency of <5%, which highlights the urgent need for more effective therapeutic strategies. We have previously shown that triptolide, a diterpenoid, is effective against pancreatic cancer cells in vitro as well as in vivo. However, triptolide is poorly soluble in water, limiting its clinical use. We therefore synthesized a water-soluble analog of triptolide, named Minnelide. The efficacy of Minnelide was tested both in vitro and in multiple independent yet complementary in vivo models of pancreatic cancer: an orthotopic model of pancreatic cancer using human pancreatic cancer cell lines in athymic nude mice, a xenograft model where human pancreatic tumors were transplanted into severe combined immunodeficient mice, and a spontaneous pancreatic cancer mouse model (KRas(G12D); Trp53(R172H); Pdx-1Cre). In these multiple complementary models of pancreatic cancer, Minnelide was highly effective in reducing pancreatic tumor growth and spread, and improving survival. Together, our results suggest that Minnelide shows promise as a potent chemotherapeutic agent against pancreatic cancer, and support the evaluation of Minnelide in clinical trials against this deadly disease. |
