Ganetespib

From Dog

Ganetespib is an immunotherapy drug which inhibits production or receptor activity of a group of heat shock proteins which are produced by solid tumors.

Heat shock protein is a molecular chaperone that normally promotes the conformational maturation and stabilization of a wide variety of cellular proteins and is usually overexpressed during malignant transformations of cells[1][2].

This drug has shown efficacy in treatment of osteosarcoma[3], mast cell tumor[4] and thyroid carcinoma[5] in dogs.

Recommended dose in dogs is 7 mg/kg once daily, extended for the period of the dog's life.

Diarrhea, lethargy, and anorexia are frequently observed side-effects at higher doses and discontinuation may result in recrudescence of tumor activity.

References

  1. Trepel J et al (2010) Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 10:537–549
  2. Wandinger SK et al (2008) The Hsp90 chaperone machinery. J Biol Chem 283:18473–18477
  3. McCleese JK et al (2009) The novel HSP90 inhibitor STA-1474 exhibits biologic activity against osteosarcoma cell lines. Int J Cancer 125:2792–2801
  4. Lin TY et al The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors. Exp Hematol 36:1266–1277
  5. London CA et al (2011) Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer. PLoS One 6(11):e27018