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The possible role of cytochrome P450s in non-small cell lung cancer therapy


Kitti Andreidesz

Lung cancer is one of the most aggressive forms of cancers
resulting in more than one million deaths yearly. From the two
types of lung cancer, non-small cell lung cancer (NSCLC)
represents about 88% of all lung cancer cases. NSCLC can
be further defined by recurrent driver mutations. The most
common mutations are KRAS and EGFR. Susceptibility to
lung cancer can be influenced by the metabolic capacity of
the lung which strongly relies on cytochrome P450 (CYP)
enzymes. Therapeutic drug response is influenced by these
enzymes also, as they metabolize many of those drugs. In
this study the expression of drug metabolizing CYPs were
measured with qPCR in primary, normal human lung
fibroblasts (NHLF) and primary, small airway epithelial cells
(SAEC) and compared to two adenocarcinoma cell lines
carrying different mutations: KRAS mutant A549 and EGFR
mutant PC9. For their role in drug metabolism CYPs may
contribute to drug resistance beside ABC transporters. For
this reason adenocarcinoma cell lines were treated with
cisplatin, a frequently used chemotherapeutic agent, then the
CYP expressions were measured and compared to the nontreated
cell lines.

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