Roswell Park Cancer Institute, Department of Cancer Prevention and Control, Buffalo, NY 14263, USA.
Expert Opin Drug Deliv. 2011 Jun;8(6):749-63. doi: 10.1517/17425247.2011.571672. Epub 2011 Apr 7.
Despite progress, chemotherapeutic response in solid malignancies has remained limited. Although initial results of the use of antiangiogenic agents in combination chemotherapy indicated an enhanced therapeutic response, recent data indicate that the surviving cancer is not only able to surmount therapy, but also actually able to adapt a more aggressive metastatic phenotype. Thus, selecting an antiangiogenic agent that is less likely to lead to tumor resurgence is a key to future therapeutic success of antiangiogenic agents in a combinatorial setting.
Against the broad spectrum of antiangiogenic agents used at present in the clinic, the putative benefits of the use of organoselenium compounds, such as methylselenocysteine (MSC), are discussed in this review.
MSC, being part of the mammalian physiology, is a well-tolerated, versatile and economical antiangiogenic agent. It downregulates multiple key upstream tumor survival markers, and enhances tumor drug delivery, at a given systemic dose of an anticancer agent, while protecting normal tissue from cytotoxic adverse effects. Further clinical trials, especially in poorly differentiated cancers, are warranted.
尽管取得了进展,但实体恶性肿瘤的化疗反应仍然有限。尽管抗血管生成药物联合化疗的初步结果表明治疗反应增强,但最近的数据表明,存活的癌症不仅能够克服治疗,而且实际上能够适应更具侵袭性的转移性表型。因此,选择不太可能导致肿瘤复发的抗血管生成药物是未来抗血管生成药物联合治疗成功的关键。
在目前临床上使用的广谱抗血管生成药物中,本文讨论了有机硒化合物(如甲基硒代半胱氨酸(MSC))的使用的潜在益处。
MSC 是哺乳动物生理学的一部分,是一种耐受性好、多功能且经济的抗血管生成药物。它下调多个关键的上游肿瘤存活标志物,并在给予抗癌药物的特定全身剂量下增强肿瘤药物输送,同时保护正常组织免受细胞毒性不良反应的影响。需要进行进一步的临床试验,特别是在分化不良的癌症中。