Trendowski Matthew
Department of Biology, Syracuse University, 107 College Place, Syracuse, NY, 13244, USA.
Drugs. 2015 Nov;75(17):1993-2016. doi: 10.1007/s40265-015-0489-4.
Through years of evolutionary selection pressures, organisms have developed potent toxins that coincidentally have marked antineoplastic activity. These natural products have been vital for the development of multiagent treatment regimens currently employed in cancer chemotherapy, and are used in the treatment of a variety of malignancies. Therefore, this review catalogs recent advances in natural product-based drug discovery via the examination of mechanisms of action and available clinical data to highlight the utility of these novel compounds in the burgeoning age of precision medicine. The review also highlights the recent development of antibody-drug conjugates and other immunotoxins, which are capable of delivering highly cytotoxic agents previously deemed too toxic to elicit therapeutic benefit preferentially to neoplastic cells. Finally, the review examines natural products not currently used in the clinic that have novel mechanisms of action, and may serve to supplement current chemotherapeutic protocols.
经过多年的进化选择压力,生物体已产生了具有显著抗肿瘤活性的强效毒素。这些天然产物对于目前癌症化疗中使用的多药治疗方案的发展至关重要,并用于治疗多种恶性肿瘤。因此,本综述通过研究作用机制和现有临床数据,梳理了基于天然产物的药物发现的最新进展,以突出这些新型化合物在蓬勃发展的精准医学时代的效用。该综述还强调了抗体药物偶联物和其他免疫毒素的最新进展,这些药物能够将以前被认为毒性太大而无法产生治疗益处的高细胞毒性药物优先递送至肿瘤细胞。最后,该综述研究了目前尚未用于临床但具有新作用机制的天然产物,这些产物可能有助于补充当前的化疗方案。