Elucidating resistance to AKT inhibition in metastatic breast cancer

AKT抑制已成为乳腺癌最有前途的靶向治疗之一。在具有通路突变的三阴性乳腺癌中，AKT抑制与紫杉醇具有实质性疗效。在ER阳性乳腺癌中，capivasertib对AKT1突变型乳腺癌以及与氟维司群联合治疗具有显著活性。然而，对临床相关耐药机制的了解非常有限。我们将使用乳腺癌患者来源的模型，包括类器官和异种移植物，来研究对AKT抑制剂获得性耐药或耐药的机制，结合来自AKT抑制剂临床试验的患者材料，来鉴定和验证耐药机制。

AKT Inhibition has emerged as one of the most promising targeted therapies for breast cancer. In triple negative breast cancer with pathway mutations, AKT inhibition has substantial efficacy with paclitaxel. In ER positive breast cancer, capivasertib has substantial activity in AKT1 mutant breast cancer and in combination with fulvestrant. Yet there is very limited understanding of clinically relevant resistance mechanisms. We will use breast cancerpatient derived models, both organoid and xenograft, to study mechanisms of acquired resistance to AKT inhibitorresistance, combined with patients' material from AKT inhibitor clinical trials, to identify and validate mechanismsof resistance.