Lewis lung carcinoma
From Wikipedia, the free encyclopedia
Lewis lung carcinoma is a hypermutated Kras/Nras–mutant cancer with extensive regional mutation clusters in its genome. A tumor that spontaneously developed as an epidermoid carcinoma in the lung of a C57BL mouse. It was discovered in 1951 by Dr. Margaret Lewis of the Wistar Institute and became one of the first transplantable tumors.[1]
Thirty-three deleterious mutations are present in 30 cancer genes including Kras, Nras, Trp53, Dcc, and Cacna1d. Cdkn2a and Cdkn2b are biallelically deleted from the genome. Five pathways (RTK/RAS, p53, cell cycle, TGFB, and Hippo) are oncogenically deregulated or affected. The major mutational processes in LLC include chromosomal instability, exposure to metabolic mutagens, spontaneous 5–methylcytosine deamination, defective DNA mismatch repair, and reactive oxygen species. Our data also suggest that LLC is a lung cancer similar to human lung adenocarcinoma.[2]
Syngeneic
According to a 2015 review article, Lewis lung carcinoma is the only reproducible syngeneic lung cancer model, meaning that it is the only reproducible lung cancer model that utilizes a transplant that is immunologically compatible. Syngeneic models have proven to be useful in predicting the clinical benefit of therapy in preclinical experiments. However, there has been criticism directed towards syngeneic model usage when attempting to translate therapies from another species to humans. For example, cancer therapies that exhibited promising results in mouse models can and have failed in clinical trials due to physiological differences in the activity of the targeted gene product. The activity of the mouse product did not translate to the activity of the human counterpart.[3]
Orthotopic
Lewis lung carcinoma can also be utilized as an orthotopic model.[3] Orthotopic models focus upon correctly modeling the tumor microenvironment by injecting or implanting tumors into the corresponding organ that they originated from (i.e. implanting a Lewis lung carcinoma into the lung of another C57BL mouse). Because of this fidelity to mimicking the tumor microenvironment, orthotopic models are considered to be more physiologically relevant in representing human tumorigenesis. However, the creation of such models is a typically more involved and technically challenging process. They also require more complex imaging modalities for data collection.[4]