The project Tankyrase Inhibition in Cancer Immunotherapy aims to bring tankyrase inhibition into clinical practice.The advancement into clinical studies will be done together with the Dutch medicinal chemistry company Merchachem and Inven2.
- This grant allows us to continue and finalize essential basic and translational research to reach our goal of getting the drug into clinical studies, says project leader Jo Waaler.
Melanoma is the most dangerous type of skin cancer and the development of immune checkpoint inhibitors represents a major breakthrough in melanoma therapy. Nevertheless, a substantial number of patients fail to respond to checkpoint pathway blockade. Checkpoint inhibitors is used in immunotherapy to “release the brakes” of the immune system. Tankyrase inhibitors counteracts resistance to checkpoint inhibition.
Scientific project summary
The project aims to bring tankyrase inhibition into clinical practice by thoroughly analyzing the mode-of-action that rules its efficacy in combination with immune checkpoint inhibition.
Our WNT signaling inhibitor development program has led to identification of a set of a highly potent and specific tankyrase inhibitors. The advance of our program to clinical studies is pursued in co-operation with the Dutch medicinal chemistry company Mercachem and Inven2.
Melanoma is the most dangerous type of skin cancer and the development of immune checkpoint inhibitors represents a major breakthrough in melanoma therapy. Nevertheless, a substantial number of patients fail to respond to checkpoint pathway blockade.
Evidence for β-catenin-mediated immune evasion is found in 13% of all cancers, 42% of primary cutaneous melanoma and a mouse melanoma model. Currently, there are no therapeutic strategies available for targeting WNT/β-catenin signaling to counteract checkpoint inhibitor resistance in melanoma. Development of new drugs, including drugs blocking WNT/ β-catenin signaling, for checkpoint inhibitor-resistant melanoma patients is clearly needed.
Preliminary results show that tankyrase inhibition attenuates WNT/β-catenin and hippo signaling pathways in a syngeneic mouse melanoma model enabling sensitivity to immune checkpoint therapy.