Walker Charles W, Böttger Stefanie A
Molecular, Cellular and Biomedical Sciences, Center for Marine Biology & Marine Biomedical Research Group, The University of New Hampshire, Durham, New Hampshire 03824, USA.
Cell Cycle. 2008 Aug;7(15):2286-9. doi: 10.4161/cc.6366. Epub 2008 May 29.
As Jessani et al.,(1) point out development of cell and animal models that accurately depict human tumorigenesis remains a major goal of cancer research. Clam cancer offers significant advantages over traditional models for genotoxic and non-genotoxic preclinical analysis of treatments for human cancers with a similar molecular basis. The naturally occurring clam model closely resembles an outbreeding, human clinical population and provides both in vitro and in vivo alternatives to those generated from inbred mouse strains or by intentional exposure to known tumor viruses. Fly and worm in vivo models for adult human somatic cell cancers do not exist because their adult somatic cells do not divide. Clam cancer is the best characterized, naturally occurring malignancy with a known molecular basis remarkably similar to those observed in several unrelated human cancers where both genotoxic and non-genotoxic strategies can restore the function of wild-type p53. To further emphasize this point of view, we here demonstrate a p53-induced, mitochondrial-directed mechanism for promoting apoptosis in the clam cancer model that is similar to one recently identified in mammals. Discerning the molecular basis for naturally occurring diseases in non-traditional models and correlating these with related molecular mechanisms responsible for human diseases is a virtually unexplored aspect of toxico-proteomics and genomics and related drug discovery.
正如杰萨尼等人（1）所指出的，开发能够准确描绘人类肿瘤发生过程的细胞和动物模型仍然是癌症研究的一个主要目标。与传统模型相比，蛤类癌症在对具有相似分子基础的人类癌症治疗进行遗传毒性和非遗传毒性临床前分析方面具有显著优势。天然存在的蛤类模型与远交的人类临床群体非常相似，并且为那些由近交小鼠品系产生或通过有意暴露于已知肿瘤病毒而得到的模型提供了体外和体内的替代选择。由于苍蝇和蠕虫的成体体细胞不分裂，所以不存在用于成人人类体细胞癌的体内模型。蛤类癌症是特征最明确的天然恶性肿瘤，其已知分子基础与在几种不相关的人类癌症中观察到的情况非常相似，在这些癌症中，遗传毒性和非遗传毒性策略都可以恢复野生型p53的功能。为了进一步强调这一观点，我们在此展示了一种在蛤类癌症模型中由p53诱导的、线粒体导向的促进细胞凋亡的机制，该机制与最近在哺乳动物中发现的一种机制相似。在非传统模型中识别天然疾病的分子基础，并将这些与导致人类疾病的相关分子机制联系起来，这实际上是毒理蛋白质组学和基因组学以及相关药物发现中一个尚未被探索的方面。
