Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Future Med Chem. 2013 Jun;5(9):1023-35. doi: 10.4155/fmc.13.63.
Despite our deepening understanding of the mechanisms of resistance and intensive efforts to develop therapeutic solutions to combat resistance, de novo and acquired tamoxifen resistance remains a clinical challenge, and few effective regimens exist to treat tamoxifen-resistant breast cancer. The complexity of tamoxifen resistance calls for diverse therapeutic approaches. This review presents several therapeutic strategies and lead compounds targeting the estrogen receptor signaling pathways for treatment of tamoxifen-resistant breast cancer, with a critical assessment of challenges and potentials regarding clinical outcome. Medicinal chemistry holds the key to effective, personalized combination therapy for tamoxifen-resistant breast cancer by making available a diverse arsenal of small-molecule drugs that specifically target signaling pathways modulating hormone resistance. These combination therapy candidates should have the desired specificity, selectivity and low toxicity to resensitize tumor response to tamoxifen and/or inhibit the growth and proliferation of resistant breast cancer cells.
尽管我们对耐药机制的理解不断加深，并且为了寻找治疗耐药的方法付出了巨大努力，但新出现的和获得性的他莫昔芬耐药仍然是一个临床挑战，并且几乎没有有效的方案可以治疗他莫昔芬耐药的乳腺癌。他莫昔芬耐药的复杂性需要多种治疗方法。这篇综述介绍了几种针对雌激素受体信号通路的治疗策略和先导化合物，用于治疗他莫昔芬耐药的乳腺癌，并对临床结果的挑战和潜力进行了批判性评估。通过提供针对调节激素耐药的信号通路的多样化小分子药物，药物化学为有效的、个性化的他莫昔芬耐药乳腺癌联合治疗提供了关键，这些联合治疗候选药物应该具有所需的特异性、选择性和低毒性，以重新使肿瘤对他莫昔芬敏感和/或抑制耐药乳腺癌细胞的生长和增殖。
