Emons G, Schally A V
Department of Obstetrics and Gynecology, Philipps University, Marburg, Germany.
Hum Reprod. 1994 Jul;9(7):1364-79. doi: 10.1093/oxfordjournals.humrep.a138714.
The use of agonistic analogues of luteinizing hormone releasing hormone (LHRH) is an established therapy for hormone-dependent metastatic pre-menopausal breast cancer. Their mechanism of action in this disease is the suppression of ovarian oestrogen production (medical castration). In the treatment of post-menopausal metastatic breast cancer, LHRH agonists also have some effect, although minor, probably through a suppression of ovarian androgen production. Convincing evidence has been accumulated that LHRH analogues can directly inhibit the proliferation of breast cancer cells in vitro. The clinical impact of these findings, however, is still controversial. Experimental data and several pilot clinical trials suggest that in epithelial ovarian cancer and sex-cord-stromal tumours of the ovary, LHRH agonists might have antitumour activity through the suppression of gonadotrophin secretion (selective medical hypophysectomy). Phase III clinical trials, evaluating this hypothesis, are in progress. Direct antiproliferative effects of LHRH analogues on epithelial ovarian cancer cells have been demonstrated in vitro. In endometrial cancer, experimental and early clinical results support the concept of a direct antiproliferative activity of LHRH analogues. Recently, potent antagonistic analogues of LHRH, devoid of relevant side-effects have become available for clinical testing. These new antagonists might be superior to agonistic LHRH analogues with respect to the rapidity and efficacy of selective medical hypophysectomy and medical castration. Modern LHRH antagonists might also permit a better exploitation of direct antitumour effects. A further therapeutic improvement in gynaecological oncology might result from a combination of LHRH agonists or antagonists with other peptide hormone analogues such as agonists of somatostatin or antagonists of bombesin/gastrin releasing peptide which have antitumour activity. Since 50% of breast cancers and 80% of epithelial ovarian cancers and endometrial cancers have high affinity binding sites for LHRH, cytotoxic LHRH analogues might provide a targeted chemotherapy, which would be more efficacious and less toxic than conventional regimens.
促黄体生成素释放激素（LHRH）激动剂类似物的使用是激素依赖性转移性绝经前乳腺癌的一种既定治疗方法。它们在这种疾病中的作用机制是抑制卵巢雌激素的产生（药物去势）。在绝经后转移性乳腺癌的治疗中，LHRH激动剂也有一定作用，尽管作用较小，可能是通过抑制卵巢雄激素的产生。已有确凿证据表明，LHRH类似物可在体外直接抑制乳腺癌细胞的增殖。然而，这些发现的临床影响仍存在争议。实验数据和一些初步临床试验表明，在卵巢上皮性癌和卵巢性索间质肿瘤中，LHRH激动剂可能通过抑制促性腺激素分泌（选择性药物垂体切除术）而具有抗肿瘤活性。评估这一假设的III期临床试验正在进行中。LHRH类似物对卵巢上皮癌细胞的直接抗增殖作用已在体外得到证实。在子宫内膜癌中，实验和早期临床结果支持LHRH类似物具有直接抗增殖活性的概念。最近，已可获得无相关副作用的强效LHRH拮抗类似物用于临床试验。就选择性药物垂体切除术和药物去势的速度和疗效而言，这些新型拮抗剂可能优于LHRH激动剂类似物。现代LHRH拮抗剂也可能更有利于发挥直接抗肿瘤作用。LHRH激动剂或拮抗剂与其他具有抗肿瘤活性的肽激素类似物（如生长抑素激动剂或蛙皮素/胃泌素释放肽拮抗剂）联合使用，可能会进一步改善妇科肿瘤的治疗效果。由于50%的乳腺癌、80%的卵巢上皮性癌和子宫内膜癌具有LHRH的高亲和力结合位点，细胞毒性LHRH类似物可能提供一种靶向化疗，比传统方案更有效且毒性更小。
