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.
- Cucurbitacins and withanolides can be successfully developed in combination with known TRAIL agonist have the potential of new cancer combination therapies without major toxicities.
- Use of the compounds with known TRAIL or agonist antibodies such as Mapatumumab or in combination with immunotherapeutic approaches for the treatment of cancer.