Induction of the TEAD Coactivator VGLL1 by Estrogen Receptor-Targeted Therapy Drives Resistance in Breast Cancer.

Resistance to endocrine therapies (ET) is common in estrogen receptor (ER)-positive breast cancer, and most relapsed patients die with ET-resistant disease. Although genetic mutations provide explanations for some relapses, mechanisms of resistance remain undefined in many cases. Drug-induced epigenetic reprogramming has been shown to provide possible routes to resistance.

T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals.

T-cell-recruiting bispecific molecule therapy has yielded promising results in patients with hematologic malignancies; however, resistance and subsequent relapse remains a major challenge. T-cell exhaustion induced by persistent antigen stimulation or tonic receptor signaling has been reported to compromise outcomes of T-cell-based immunotherapies. The impact of continuous exposure to bispecifics on T-cell function, however, remains poorly understood.