Letter to the editor regarding the review article: Yamada T, Cohen SM, Lake BG. The modes of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR) and the peroxisome proliferator-activated receptor alpha (PPARα) are not relevant to human cancer risk: an updated critical evaluation. Crit Rev Toxicol. 2025;55(5):549-586. doi: 10.1080/10408444.2025.2513332.