Department of Endocrine and Breast Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, PR China.
Med Hypotheses. 2013 Apr;80(4):441-6. doi: 10.1016/j.mehy.2012.12.037. Epub 2013 Jan 31.
Chemosensitization means enhancing the sensitivity of tumor cells to chemotherapy with certain methods for better efficacy. Tumor progression depends on stimulation of multiple hormones, decrease in hormones during chemotherapy induces G0/G1 arrest of tumor cells, which may be the main cause for chemoresistance. Some of the choriocarcinoma and testicular tumors are curable with chemotherapy only, underlying mechanism may refer high level of human chorionic gonadotropin, which has thyroid stimulating hormone like effect and even induce hyperthyroidism in these patients. Some of these patients usually have high levels of thyroid hormones or suffer thyroid crisis during chemotherapy. Possibly owning to the proliferative or metabolic promotion effect of thyroid hormones and/or other endocrine hormones, which can promote tumor cells in G0 phase metabolizing actively or stepping into division cycle again, tumors are more sensitive to chemotherapy. Both endocrinotherapy and chemotherapy are major therapies for tumor, traditional endocrinotherapy suppresses tumor progression through decreasing tumor-dependent hormones or competitively combining and blocking hormone receptors. While, chemotherapy mostly killed tumor cells that proliferate actively, because tumor cells retardant in G0 phase by endocrinotherapy are no more sensitive to chemotherapy, endocrinotherapy cannot be concurrently used with chemotherapy. Nevertheless, decrease in hormones during chemotherapy is similar to concurrently using endocrinotherapy and chemotherapy. It has been found in some basic researches that some chemotherapeutics concurrently combined with endocrine hormones can achieve better efficacy compared with chemotherapy only. It is therefore hypothesized in this article that decrease in hormones during chemotherapy causes cell cycle arrest and renders tumor cells insensitive to chemotherapy; addition of endocrine hormones to mimic the hormones and microenvironment changes during chemotherapy for patients with choriocarcinoma or testicular tumor-curable with chemotherapy only, will rescue tumor cells from cell cycle arrest rendering them sensitive to chemotherapy. This new combinative therapy of concurrently using endocrine hormones and chemotherapy is defined as choriocarcinoma-mimic chemotherapy or neo-endocrinochemotherapy to distinguish the routine term of endocrinochemotherapy and is expected to be a novel approach to enhance chemotherapeutic efficacy in clinic.
化疗增敏是指采用一定的方法增强肿瘤细胞对化疗的敏感性,以提高疗效。肿瘤的进展依赖于多种激素的刺激,化疗过程中激素的下降会导致肿瘤细胞停滞在 G0/G1 期,这可能是化疗耐药的主要原因。一些绒毛膜癌和睾丸肿瘤仅用化疗即可治愈,其潜在机制可能与高水平的人绒毛膜促性腺激素有关,该激素具有促甲状腺激素样作用,甚至会导致这些患者发生甲状腺功能亢进。这些患者中的一些人在化疗过程中通常甲状腺激素水平较高或发生甲状腺危象。可能是由于甲状腺激素或其他内分泌激素的促增殖或代谢作用,可以促进 G0 期肿瘤细胞积极代谢或再次进入分裂周期,肿瘤对化疗更敏感。内分泌治疗和化疗都是肿瘤的主要治疗方法,传统的内分泌治疗通过降低肿瘤依赖性激素或竞争性结合和阻断激素受体来抑制肿瘤进展。而化疗主要杀死增殖活跃的肿瘤细胞,因为内分泌治疗使 G0 期肿瘤细胞迟缓,对化疗不再敏感,因此不能与化疗同时使用。然而,化疗过程中激素的下降类似于同时使用内分泌治疗和化疗。一些基础研究发现,一些化疗药物与内分泌激素同时联合使用比单独化疗效果更好。因此,本文提出假设,即化疗过程中激素的下降导致细胞周期停滞,使肿瘤细胞对化疗不敏感;向仅用化疗即可治愈的绒毛膜癌或睾丸肿瘤患者添加内分泌激素,模拟化疗期间的激素和微环境变化,可使肿瘤细胞从细胞周期停滞中恢复,对化疗敏感。这种同时使用内分泌激素和化疗的新联合治疗方法被定义为绒毛膜癌模拟化疗或新型内分泌化疗,以区别于常规的内分泌化疗术语,并有望成为提高临床化疗疗效的新方法。