The first keynote lecture of the 2021 ESMO annual meeting was given by Nobel laureate, Dr. William Kaelin of the Dana-Farber Cancer Institute in Boston. Dr. Kaelin on the reemerging principles of cancer therapy and how combination therapies are more effective in long-term cancer care.

To begin with, Dr. Kaelin explained how the most successful approaches in cancer treatment are when an initial, truncal genetic event is targeted instead of the branch mutations that occur later in a tumor’s evolution. Some of the successfully approved precision oncology drugs have been those that targeted proteins that have a good genetic validation as well as a fairly deep biological understanding.

However, there have been many that have remained undruggable despite extensive evaluation. For those, it would be better to exploit epistatic relationships by targeting druggable critical downstream effectors. There is also renewed interest in developing allosteric inhibitors that can indirectly inactive proteins through protein folding changes. Recently, various small molecule degraders have also entered the scene.