TYMS and cancer: Over six decades of research have positioned TS as a cornerstone of antimetabolite-based chemotherapy.1,63 The enzyme's structural features, multifaceted regulation, and integration into folate metabolism provide multiple opportunities for therapeutic intervention.2,62,103,104 However, the adaptability of cancer cells through TS overexpression and compensatory pathway activation continues to limit the long-term success of current inhibitors.105