A naturally occurring cancer with molecular connectivity to human diseases.
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.
Walker
Charles W
CW
Molecular, Cellular and Biomedical Sciences, Center for Marine Biology & Marine Biomedical Research Group, The University of New Hampshire, Durham, New Hampshire 03824, USA. cwwalker@cisunix.unh.edu
Böttger
Stefanie A
SA
D000820:Animal Diseases / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D003386:Brachyura / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004194:Disease / Q000209:etiology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D011725:Pyridines / Q000627:therapeutic use; D015398:Signal Transduction / Q000235:genetics*; D013844:Thiazoles / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D011725:Pyridines; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; C080352:mortalin; C097880:MKT 077