Breast cancer is the most commonly occurring malignancy in women and the second most common cause of cancer-related deaths. ER+breast cancer constitutes approximately 70% of all breast cancer cases. The standard of care for ER+breast cancer involves estrogen antagonists such as tamoxifen or fulvestrant in combination with CDK4/6 inhibitors such as palbociclib. However, these treatments are often not curative, with disease recurrence and metastasis being responsible for patient mortality. Overexpression of the epigenetic regulator, BRD4, has been shown to be a negative prognostic indicator in breast cancer, and BET family inhibitors such as ARV-825 and ABBV-744 have garnered interest for their potential to improve and prolong the response to current therapeutic strategies. The current work examined the potential of utilizing ARV-825 and ABBV-744 to increase the effectiveness of tamoxifen or fulvestrant plus palbociclib. ARV-825 was effective in both p53 wild-type (WT) breast tumor cells and in cells lacking functional p53 either alone or in combination with tamoxifen, while the effectiveness of ABBV-744 was limited to fulvestrant plus palbociclib in p53 WT cells. These differential effects may be related to the capacity to suppress c-Myc, a downstream target of BRD4.
乳腺癌是女性最常见的恶性肿瘤，也是癌症相关死亡的第二大常见原因。ER阳性乳腺癌约占所有乳腺癌病例的70%。ER阳性乳腺癌的标准治疗方案包括他莫昔芬或氟维司群等雌激素拮抗剂联合哌柏西利等CDK4/6抑制剂。然而，这些治疗通常无法根治疾病，复发和转移是导致患者死亡的主要原因。表观遗传调控因子BRD4的过度表达已被证明是乳腺癌的不良预后指标，而ARV-825和ABBV-744等BET家族抑制剂因其可能改善和延长当前治疗策略的疗效而受到关注。本研究探讨了利用ARV-825和ABBV-744提高他莫昔芬或氟维司群联合哌柏西利疗效的潜力。ARV-825在p53野生型乳腺癌肿瘤细胞和缺乏功能性p53的细胞中均有效，无论是单独使用还是与他莫昔芬联合使用；而ABBV-744的疗效仅限于在p53野生型细胞中与氟维司群联合哌柏西利使用。这些差异效应可能与抑制BRD4下游靶点c-Myc的能力有关。
肿瘤(癌症)患者之家