BLR&D Research Career Scientist Award

苯扎鲁胺被批准用于治疗转移性去势抵抗前列腺癌(CRPC)。 尽管这些进展提供了生存增加，但CRPC仍然没有治愈方法。抵抗力 苯扎鲁胺经常发生，其作用机制尚不完全清楚。因此，剖析 CRPC耐药的特异性适应/耐药途径及鉴定新基因 针对这些途径的策略将极大地影响慢性前列腺癌患者的护理。LIN28，一种RNA 结合蛋白是一种诱导细胞增殖和转化的癌基因。LIN28抑制let-7， 一种参与抑制雄激素信号的miRNA。我们的初步数据表明，LIN28促进了 去势抵抗前列腺癌进展并与雄激素治疗抵抗相关 治疗。LIN28在前列腺癌中表达上调，其表达与前列腺癌的分期有关。 总之，这些研究强调了LIN28在促进前列腺癌进展和 对苯扎鲁胺的耐药性，提示靶向LIN28可能提供新的治疗机会 前列腺癌。这项提议将确定Lin28在对苯扎鲁胺的抗性中的作用，并探索 以林28为靶点克服抗性的潜力。这项建议的具体目的是：1.审查 LIN28在苯扎鲁胺耐药中的作用。2.确定分子机制 LIN28介导的对苯扎鲁胺的抗性。3.评估以LIN28为目标克服阻力 接受苯扎鲁胺治疗。拟议的研究将识别和描述一种新的抗性 涉及LIN28的机制和评价靶向LIN28克服对苯扎鲁胺治疗的耐药性。

Enzalutamide was approved for the treatment of metastatic castration resistant prostate cancer (CRPC). Despite these advances that provide survival gains, there is still no cure for CRPC. Resistance to enzalutamide occurs frequently and the mechanisms are incompletely understood. Hence, dissecting the specific adaptive/resistant pathways that are responsible for drug resistance in CRPC and identifying novel strategies targeting these pathways will dramatically impact the care of men with CRPC. Lin28, a RNA binding protein, acts as an oncogene inducing cell proliferation and transformation. Lin28 suppresses let-7, a miRNA involved in suppressing androgen signaling. Our preliminary data suggest that Lin28 promotes castration resistant prostate cancer progression and is associated with resistance to androgen ablation treatment. Lin28 is upregulated in prostate cancer and its expression correlates with advanced tumor stage. Together, these studies underscore the importance of Lin28 in promoting prostate cancer progression and resistance to enzalutamide, suggesting that targeting Lin28 may provide novel therapeutic opportunities for prostate cancer. This proposal will determine the roles of Lin28 in resistance to enzalutamide, and explore the potential of targeting Lin28 to overcome resistance. The specific aims of this proposal are: 1. Examine the roles of Lin28 in the development of resistance to enzalutamide. 2. Determine molecular mechanisms underlying Lin28-mediated resistance to enzalutamide. 3. Evaluate targeting Lin28 to overcome resistance to enzalutamide treatment. The proposed studies will identify and characterize a novel resistance mechanism involving Lin28 and evaluate targeting Lin28 to overcome resistance to enzalutamide treatment.