Genetic editing has proven to be very effective in vivo or in vitro to model pathological conditions and decipher underlying molecular mechanisms.
Here we took advantage of genetic tools (Lentiviruses) to introduce KRAS and TP53 oncogenes into human primary bronchial cells to induce in vitro lung cancer starting from healthy donors.
Similar genetic modification strategies (CRISPR) can be used to model on demand any human respiratory pathological condition relying on genetic alterations (e.g. Cystic Fibrosis).
Current models suggest that early cancer development involves mutations in genes driving cell proliferation (KRAS) and DNA damage response (TP53). Here we propose a version of OncoCilAir™ microtissue where naïve primary human epithelial bronchial cells have been directly genetically modified to express KRAS or/and TP53 mutants in order to recapitulate the cascade of events leading to lung cancer.
Thanks to OncoCilAir™ long lifetime (months), it is possible to follow the growth of different mutant combinations and to test the effect of various anticancer therapies
Of note, it is possible to build the model starting from bronchial cells coming from specific donors, like smokers, and thus benefit of relevant genetic and epigenetic background shaped by years of active smoking.
Standard OncoCilAir™ endpoints can be measured throughout the treatment: