The Pecking Order of TGF-β

Jun 7, 2024

How unintentionally ironic that the phrase “winner, winner, chicken dinner!” is used to celebrate a victory, at least in casinos, considering that had we lived 240-66 million years ago, carnivorous dinosaurs, the ancestors of modern-day chickens, might have exclaimed, “winner, winner, human dinner!” after encountering feeble, slow, awkward, and bipedal us.

Also ironic is that the word chicken is slang for weakness, cowardice, and fear given that chickens will fight fiercely to protect their flock.

Chickens always form a pecking order or dominance hierarchy, which is strictly enforced and maintained. A strictly enforced pecking order is also present on a biochemical level in all species including chickens with chemical messengers or cytokines, many of which have been around well before the time of the dinosaurs.

One of the most dominant cytokines, which ‘rules the roost’, and wears many hats in growth and development, inflammation and repair and host immunity is known as transforming growth factor-beta (TGF-β).

Crafty cancer cells co-opt TGF-β to help them grow and progress not least because TGF-β overrides the efficacy of immunotherapies like checkpoint inhibitors. Read more about the TGF-β in this EpicentRx-authored manuscript from Future Oncology entitled TGF-β: the apex predator of immune checkpoints here.

Lead EpicentRx therapy, AdAPT-001, expresses a TGF-β trap that binds to and neutralizes TGF-β, which based on current clinical data makes checkpoint inhibitors more active in several treatment-resistant tumors like sarcoma, and triple negative breast cancer (TNBC).

If AdAPT-001 continues to demonstrate exceedingly promising activity both alone and in combination with checkpoint inhibitors, we will need to coin a new phrase: “winner, winner, no TGF-β dinner.”