NCI-H2122 Cells

The NCI-H2122 cell line is a human non-small cell lung cancer (NSCLC) model derived from an adenocarcinoma patient. It is notable for its harboring of a KRAS G12C mutation, a hallmark of NSCLC that leads to constitutive activation of the MAPK signaling pathway. This cell line is extensively used in studies focusing on therapeutic interventions targeting KRAS G12C and associated downstream pathways, particularly those involving MEK and ERK inhibitors. Research utilizing NCI-H2122 has highlighted its role in understanding drug resistance mechanisms and in optimizing combination therapies.

Preclinical studies using the NCI-H2122 cell line have demonstrated its utility in exploring resistance to MAPK pathway inhibitors. For instance, CRISPR screening approaches have identified MAPK7 (ERK5) as a critical mediator of pathway reactivation following MEK inhibition, suggesting potential combination strategies using MEK inhibitors like cobimetinib and MAPK7 inhibitors. The line also serves as a model for evaluating the efficacy of small molecule inhibitors, including those targeting PI3K and BRAF, which are relevant in combination with KRAS-specific treatments.

NCI-H2122 is also employed in investigating metabolic vulnerabilities in NSCLC. Studies have implicated serine biosynthesis and the folate cycle as metabolic pathways contributing to resistance against targeted therapies, such as BRAF inhibitors. Metabolic modulators like methotrexate and serine-deprivation strategies have been tested on this cell line, providing insights into overcoming drug resistance and identifying new metabolic targets for therapeutic exploitation.