Berstein Lev M
Laboratory of Oncoendocrinology, Prof. N. N. Petrov Research Institute of Oncology, Pesochny, St Petersburg 197758, Russian Federation.
Cancer Lett. 2005 Jun 28;224(2):203-12. doi: 10.1016/j.canlet.2004.11.011. Epub 2004 Dec 13.
Factors predisposing hormone-dependent tissues to the development of tumors coincide, at least partly, with hormonal-metabolic promoters (like insulin resistance, glucose intolerance, visceral obesity, etc.) of other main non-communicable diseases. This important knowledge poses the question of whether the same approach which is applied for prevention/treatment of a metabolic syndrome and the associated endocrine disorders might also be used in preventive and therapeutic oncology. Whereas an answer to this question remains controversial and is based mainly on experimental evidence, there is accumulating clinical data suggesting a practical significance of such a strategy, even though it is not to be considered as directly cytostatic. Among the many drugs under discussion, three groups of medicines (statins, antidiabetic biguanides, and thiazolidinediones) are the most attractive. The concept of metabolic rehabilitation is proposed and used practically in an adjuvant setting for the correction of the above-mentioned endocrine-metabolic disorders commonly found in cancer patients. The current use and aim of this approach is to improve the survival of patients and limit cancer progression. Nonetheless, it also appears potentially useful as a neoadjuvant therapy as well as a prophylactic treatment earlier in life for specific groups of people with hormone-associated enhanced oncological risk. It seems possible that certain hypolipidemic and antidiabetic medicines with pleiotropic effects might be combined with traditional antisteroid prevention/therapeutic approaches in routine clinical situations as well as for overcoming resistance to standard cancer hormonal therapies including receptor-negative cases. Characteristic at the end of the 20th and at the beginning of the 21st century is an epidemic of diabetes and obesity, which might further increase the incidence of certain cancers. This makes it timely to apply hypolipidemic and antidiabetic drugs (in combination with reasonable dieting, increased physical fitness, and an in-depth knowledge of drug-gene interactions) as an approach warranting further study.
使激素依赖组织易患肿瘤的因素,至少部分地与其他主要非传染性疾病的激素 - 代谢促进因素(如胰岛素抵抗、葡萄糖不耐受、内脏肥胖等)相吻合。这一重要知识引发了一个问题,即用于预防/治疗代谢综合征及相关内分泌紊乱的相同方法,是否也可用于肿瘤的预防和治疗。尽管对这个问题的答案仍存在争议,且主要基于实验证据,但越来越多的临床数据表明这种策略具有实际意义,即便它不能被视为直接的细胞抑制作用。在众多讨论中的药物里,有三类药物(他汀类药物、抗糖尿病双胍类药物和噻唑烷二酮类药物)最具吸引力。代谢康复的概念已被提出,并实际用于辅助治疗中,以纠正癌症患者中常见的上述内分泌 - 代谢紊乱。这种方法目前的用途和目标是提高患者的生存率并限制癌症进展。然而,它作为新辅助治疗以及对特定激素相关肿瘤风险增加人群在生命早期的预防性治疗似乎也有潜在用途。在常规临床情况下,以及在克服对包括受体阴性病例在内的标准癌症激素疗法的耐药性方面,某些具有多效性的降血脂和抗糖尿病药物似乎有可能与传统的抗类固醇预防/治疗方法相结合。20世纪末和21世纪初的特点是糖尿病和肥胖症的流行,这可能会进一步增加某些癌症的发病率。这使得及时应用降血脂和抗糖尿病药物(结合合理饮食、增加体能锻炼以及深入了解药物 - 基因相互作用)成为一种值得进一步研究的方法。