Modeling cancer patient populations in mice: Complex genetic and environmental factors

Abstract

Genetic differences among individuals contribute to differential susceptibility to cancer and, undoubtedly, to variable efficacy and toxicity of pharmacological-based therapeutics. Many of the specific molecular processes involved in human tumorigenesis have been elucidated and accurately modeled in mice. However, the current models used for drug testing do not accurately predict how new treatments will fare in clinical trials. More sophisticated models that treat cancer as a complex disease present within heterogenous patient populations will provide better predictive power to identify patients that may benefit from specific therapies or that may develop potential drug-induced toxicities.

Pancreatic Cancer Induced by In Vivo Electroporation-Enhanced Sleeping Beauty Transposon Gene Delivery System in Mouse

“…Each mouse was injected with 7.4 MBq (0.2 mCi) and 37 MBq (1 mCi) 18 F-FDG into the tail vein, and 10-minute static PET scans were obtained. After a high-performance liquid chromatography purification, the mean (SD) radiochemical purity was 98% (1.2%).…”

Pro-Oncogenic and Anti-Oncogenic Pathways: Opportunities and Challenges of Cancer Therapy

“…Tumorigenic gene mutations can also be induced by harmful environmental factors, such as tobacco overusage and UV exposure [6–8]. On the other hand, cancer development can be viewed from the point of evolution, in which case, genetic drifting followed by selection acting upon growth-control genes by chance may be sufficient to introduce oncogenic mutations that cause malignant transformation [9,10].…”

Sleeping Beauty transposon system harboring HRAS, c-Myc and shp53 induces sarcomatoid carcinomas in mouse skin

“…Its ability to achieve long-term in vivo expression suggests that the somatic integration of oncogenes using SB is a feasible approach to the development of molecularly defined tumorigenic mouse models (4). Although xenograft models and genetically engineered mice are able to mimic human cancer progression (5), the present mouse model systems do not correspond to humans with regard to genetic backgrounds (i.e., different genetic variants, genetic mutations and subsequent protein expression) (6–8). A hallmark of human cancer is genetic complexity, meaning a number of different mutations are commonly involved (9).…”