Use of Cucurbitacins and Withanolides for the Treatment of Cancer

Certain members of the cucurbitacin and Withanolide family have been identified that can sensitize some tumor cell lines to cell death (apoptosis) on subsequent exposure of the cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL "death receptors". These PARAS include TRAIL itself, and agonist antibodies to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death receptor 5 (DR5, TRAIL-R2). 

The protein TRAIL has a very interesting characteristic that it can preferentially cause death of cancer cells whereas normal non-transformed cells are unaffected.  Thus use of TRAIL or agonist antibodies to its so-called "death receptors" has been a current focus in cancer therapy. 

Competitive Advantages:

• Cucurbitacins and withanolides can be successfully developed in combination with known TRAIL agonist have the potential of new cancer combination therapies without major toxicities.

Commercial Applications:

• Use of the compounds with known TRAIL or agonist antibodies such as Mapatumumab or in combination with immunotherapeutic approaches for the treatment of cancer.