Selective Induction of Estrogen Receptor-Dependent Stress Signaling as a Therapeutic Strategy in Resistant Breast Cancer

Estrogen receptor alpha (ERα) is the defining therapeutic target in hormone receptor-positive breast cancer, yet acquired resistance remains a persistent barrier to durable clinical benefit. Patent application WO 2026/039467 A1 discloses small molecules that activate an anticipatory unfolded protein response (a-UPR) through ERα, converting receptor engagement into selective cytotoxic stress. This mechanism diverges fundamentally from classical antagonism or degradation and demonstrates preferential activity in ERα-positive tumor models─offering a conceptually distinct strategy for overcoming endocrine resistance.