NCI-H1792 — A KRAS-Mutant Lung Adenocarcinoma Model for Oncology Research

Introduction

NCI-H1792, also known as H1792, H-1792, and NCIH1792 (Cellosaurus accession CVCL_1495), is a well-characterised human non-small cell lung cancer (NSCLC) cell line established from a lung adenocarcinoma pleural effusion. The line was generated as part of the systematic NCI lung cancer cell line programme and was catalogued in the NCI-Navy Medical Oncology Branch cell line database [1]. Carrying an oncogenic KRAS G12C mutation alongside a homozygous TP53 splice-donor mutation and a heterozygous CDKN2A nonsense mutation, NCI-H1792 recapitulates the genomic complexity of human lung adenocarcinoma. Researchers have used this model extensively to investigate KRAS signalling, apoptotic pathway regulation, mTOR biology, and responses to novel anticancer compounds. The cell line is included in flagship genomic initiatives such as the Cancer Cell Line Encyclopedia (CCLE) and the NCI RAS mutant KRAS panel, underscoring its broad utility in translational oncology.

Key Takeaways

• Origin: Derived from a pleural effusion of a lung adenocarcinoma patient; part of the NCI lung cancer cell line series.
• Key mutations: Carries oncogenic KRAS G12C (heterozygous), a homozygous TP53 splice-donor mutation, and a heterozygous CDKN2A nonsense mutation (p.Trp110Ter).
• Genomic resources: Included in the CCLE, NCI RAS mutant KRAS panel, and Cancer Dependency Map, with extensive multi-omics annotation.
• Research uses: Widely applied in studies of KRAS effector biology, apoptosis, mTOR signalling, drug resistance, and 3D tumour models.
• Adherent growth: Grows as an adherent monolayer with epithelial morphology in RPMI 1640-based medium.
• LKB1 wild-type: Retains wild-type LKB1 expression, making it a useful reference against LKB1-null NSCLC lines such as A549.

What is NCI-H1792?

NCI-H1792 was established from the pleural effusion of a 50-year-old male patient diagnosed with lung adenocarcinoma. The cell line was developed as part of the NCI-Navy Medical Oncology Branch's systematic effort, beginning in 1976, to build a comprehensively annotated bank of human cancer cell lines for use as preclinical research tools [1]. This initiative later expanded into the NCI cell line database, which has been described as a foundational resource for lung cancer biology over more than four decades [2]. The cell line displays epithelial morphology and grows as an adherent monolayer, and reported doubling times range from approximately 32 to 45 hours across published datasets, making it experimentally tractable for a wide range of assays.

At the molecular level, NCI-H1792 carries a heterozygous KRAS G12C mutation (c.34G>T), a homozygous TP53 splice-donor mutation (c.672+1G>A), and a heterozygous CDKN2A nonsense mutation (p.Trp110Ter, c.330G>A). Note that catalogue sources differ on KRAS zygosity: Cellosaurus, COSMIC, and DepMap annotate the G12C allele as heterozygous, and functional studies describing NCI-H1792 as carrying a single endogenous mutant KRAS allele support this [10], whereas some vendor documentation lists it as homozygous. The TP53 splice-site lesion was among the diverse p53 mutations catalogued across a large panel of NSCLC lines in an early characterisation study [3]. The cell line shows wild-type LKB1 expression [6] and retains intact RB-family protein expression [4], features that distinguish it from other commonly used NSCLC lines. NCI-H1792 is microsatellite-stable and is classified as European ancestry (North European 59.2%, South European 34.9%) based on genome-wide genotyping data [5].

Cell Culture Information

NCI-H1792 – low confluency

NCI-H1792 – high confluency

Advantages of NCI-H1792

NCI-H1792 occupies a unique niche among NSCLC cell lines because of its well-defined KRAS G12C mutation combined with wild-type LKB1 status and intact RB-family expression. This genetic combination makes it highly complementary to lines such as A549 Cells, which carry a different KRAS G12S allele and lack LKB1. The two lines are not isogenic — they derive from different patients — but the contrast between them has proven scientifically valuable: studies comparing LKB1 wild-type and mutant NSCLC lines have used NCI-H1792 as the wild-type reference to probe the LKB1–AMPK–mTOR signalling axis [6]. Pairing the two lines therefore provides a practical, if not genetically matched, contrast for mechanistic work on LKB1-dependent signalling.

The cell line's inclusion across multiple major multi-omics consortia — including the CCLE, the Cancer Dependency Map, and the COSMIC cell lines project — means that extensive reference datasets are publicly available. Researchers can immediately contextualise in-house drug-sensitivity, proteomic, or transcriptomic results against thousands of other cancer lines. Every batch of Cytion's NCI-H1792 Cells is released with a lot-specific Certificate of Analysis documenting STR authentication, mycoplasma testing, and post-thaw viability, so the exact figures for a given vial should be taken from the CoA supplied with that lot.

NCI-H1792 is also a validated model for three-dimensional tumour spheroid culture. The line has been shown to self-organise into structured spheroids when embedded in collagen scaffolds alongside cancer-associated fibroblasts, enabling realistic modelling of the tumour microenvironment and epithelial-to-mesenchymal transition [7]. This versatility means the line supports both classical 2D drug screening and more sophisticated 3D organotypic assays within the same laboratory workflow.

Limitations of NCI-H1792

Because NCI-H1792 was derived from a pleural effusion rather than primary tumour tissue, the biological properties of the line may reflect selection pressures associated with the metastatic microenvironment. Like all established cell lines, it lacks the stromal, immune, and vascular components present in vivo. Researchers studying tumour–stroma interactions must supplement single-line experiments with co-culture models or in vivo validation.

The homozygous TP53 splice-donor mutation in NCI-H1792 means that normal p53-dependent stress responses are absent. This limits the cell line as a model for studying wild-type p53 biology and may confound interpretation of apoptosis studies that rely on p53-mediated transcriptional activation. Investigators should be aware that drug-induced cell death in this line likely proceeds through p53-independent pathways, as demonstrated in studies examining Bcl-xL inhibition in combination with irradiation [8].

The CDKN2A lesion is a nonsense mutation (p.Trp110Ter) that truncates the p16^INK4a reading frame, so the line should not be treated as CDKN2A-proficient when designing or interpreting cell-cycle arrest experiments — particularly those involving CDK4/6 inhibition. In addition, published doubling-time estimates for NCI-H1792 differ appreciably between datasets (approximately 32.6 hours in one large-scale screen and 45 hours in another), so growth-rate-dependent assay windows, seeding densities, and endpoint timings should be established empirically in each laboratory rather than taken from a single literature value.

Applications

KRAS Signalling and Targeted Therapy

The oncogenic KRAS G12C allele makes NCI-H1792 one of the most widely used models for dissecting KRAS effector engagement in lung adenocarcinoma. Yuan et al. performed an arrayed combinatorial siRNA screen across 92 cancer cell lines, knocking down 41 KRAS effector nodes, and demonstrated that despite heterogeneity across cell lines, two major subtypes of KRAS-mutant cancers could be distinguished by their effector dependencies [9]. NCI-H1792 was among the lines used to define these subtypes, contributing to a framework for selecting therapeutic vulnerabilities in KRAS-driven NSCLC.

Farnsworth et al. investigated acquired MEK inhibitor resistance in KRAS-mutant lung adenocarcinoma and identified a phenomenon they termed "addiction to sustained ERK suppression." To test whether RB status governs this behaviour, the authors generated isogenic clones of NCI-H1792 and NCI-H358 carrying CRISPR/Cas9-mediated RB1 knockout [10]. Contrary to earlier reports based on transient knockdown, RB1 loss produced only modest increases in trametinib IC₅₀, and knockout and control clones acquired trametinib resistance at the same rate; re-expressing RB1 in knockout cells had no effect. The drug-addicted phenotype itself arose in an H358 clone and was driven by amplification of the mutant KRAS allele rather than by RB status. NCI-H1792 was also used to confirm the generalisability of that mechanism: doxycycline-induced overexpression of KRAS^G12C reduced viability in NCI-H1792, and this loss of viability was rescued by low-dose trametinib or sotorasib (AMG 510). The value of NCI-H1792 in this work therefore lies in providing a well-defined isogenic RB1 series and a second KRAS G12C background for validating ERK-hyperactivation toxicity, not in demonstrating an RB1-dependent resistance mechanism.

The AP-1 transcription factor JunD has also been implicated in RAS-driven lung cancer. Using conditional deletion in a K-Ras^G12D mouse model of lung adenocarcinoma, Ruiz et al. showed that loss of c-Jun increased tumour burden whereas deletion of JunD abolished Ras-driven tumorigenesis, identifying JunD — rather than c-Jun — as the AP-1 family member required for Ras-induced lung cancer [30]. Separately, Wang et al. applied the ConSig algorithm to lung cancer transcriptome sequencing data and identified a novel R3HDM2–NFE2 gene fusion in the NCI-H1792 cell line; genomic rearrangement at the NFE2 locus was detected in 2 of 76 primary lung tumours, and NFE2 knockdown reduced proliferation and invasion of NCI-H1792 cells [11].

Apoptosis and Cell Death Mechanisms

NCI-H1792 has served as a productive model for evaluating pro-apoptotic compounds in NSCLC. The thiazolidin compound MMPT was characterised in H1792 cells and shown to inhibit growth in a dose- and time-dependent manner, triggering apoptosis through activation of caspase-3, caspase-6, and caspase-8 — but not caspase-9 — via the Fas-mediated pathway [12]. A subsequent study extended these findings and demonstrated that MMPT acts as a reactive oxygen species generator in A549 Cells, inducing apoptosis through glutathione depletion, further validating the compound's broad antineoplastic activity across NSCLC models [13].

Sodium 4-phenylbutyrate (PB) induced apoptosis in NCI-H1792 and NCI-H460 cells specifically through activation of the JNK MAP kinase pathway, while causing G1 arrest in other NSCLC lines such as A549 Cells and SK-LU-1 Cells, demonstrating cell-line-specific responses to the same agent [14]. This cell-type selectivity highlights NCI-H1792 as a useful comparator when profiling novel compounds across heterogeneous NSCLC models.

Bcl-2 family proteins represent another apoptotic axis studied in NCI-H1792. Roa et al. tested the BH3-domain antagonist BH3I-1 in combination with gamma irradiation and demonstrated that blockade of Bcl-xL sensitised NCI-H1792 cells — which carry mutant p53 — to radiation-induced cell death, an effect not seen in p53 wild-type NCI-H460 cells [8]. Propofol, an intravenous anaesthetic, was shown to inhibit NCI-H1792 cell viability and induce apoptosis by upregulating miR-486 expression, with downstream increases in FOXO1, FOXO3, the BH3-only protein Bim, and activated caspase-3; a miR-486 inhibitor reversed these effects [15]. Collectively, these studies position NCI-H1792 as a reliable model for evaluating apoptosis-inducing strategies in p53-mutant lung cancer.

mTOR and LKB1–AMPK Pathway Biology

Wild-type LKB1 expression in NCI-H1792 makes it a valuable reference line for studying the LKB1–AMPK–mTOR signalling axis in NSCLC. Dong et al. demonstrated that energy stress induced by 2-deoxyglucose augmented AMPK phosphorylation in NCI-H1792, and that this response was coupled to suppression of mTOR substrates 4E-BP1 and S6K, consistent with intact LKB1 function acting as a negative regulator of mTOR activity [6]. The study highlighted the importance of LKB1 status as a determinant of cellular energy-sensing capacity in lung cancer cell lines.

A follow-up study by Xiao et al. examined whether LKB1 inactivation sensitises NSCLC cells to mTOR inhibitors such as rapamycin and everolimus. Although LKB1-mutant lines showed higher basal mTOR activity than NCI-H1792, the LKB1 status did not predict differential sensitivity to mTOR inhibition in vitro, contrasting with observations made in endometrial cancer [16]. These findings underscore the tissue-specific context dependency of LKB1–mTOR interactions and caution against translating observations from other cancer types directly to NSCLC.

Drug Resistance and Transcriptomic Profiling

NCI-H1792 has been used as a parental line to generate drug-resistant sub-lines. Raungrut et al. derived carboplatin-resistant (H1792/Car) and paclitaxel-resistant (H1792/Pac) clones through prolonged drug selection, achieving 10.7-fold and 5.6-fold resistance increases, respectively, over six months. Transcriptome sequencing of these resistant lines identified CSF3 as a hub gene upregulated across both resistant variants, proposing it as a potential biomarker for carboplatin/paclitaxel doublet regimens [17]. This work validates NCI-H1792 as a tractable system for generating and characterising chemotherapy resistance models.

MicroRNA biology in NCI-H1792 has been explored in multiple contexts. Geater et al. examined the biological functions of miR-145 in the NSCLC cell lines A549 and NCI-H1792, showing that miR-145 reduced proliferation via cell cycle arrest, and reported on its diagnostic and prognostic value when measured as a serum biomarker in a clinical cohort of 215 patients [18]. NCI-H1792 has also served as a negative control in pharmacological work: Okada et al. showed that dapagliflozin causes loss of cell adhesion and ADAM10-dependent ectodomain shedding of DDR1 in SGLT2-positive, UGT1A9-negative HCT116 cells, whereas NCI-H1792 — which expresses neither SGLT2 nor UGT1A9 — was resistant to these adhesion-related effects [19]. This makes NCI-H1792 a useful comparator for defining the transporter dependency of SGLT2 inhibitor effects in cancer cells.

Systematic migration studies have also included NCI-H1792. Pal et al. developed the MigExpress platform, combining transcriptome and proteome profiling with quantitative migration measurements across a panel of 54 NSCLC cell lines, and identified and validated FLNC, DSE, CPA4, TUBB6, and BICC1 as migration control factors whose expression also correlated with patient survival [31]. In more targeted work, SKP2, a component of the ubiquitin–proteasome system, was silenced in NCI-H1792 using siRNA, which reduced proliferation to 28% of control levels and increased the cyclin-dependent kinase inhibitor p27, inversely proportional to SKP2 knockdown efficiency [20]. Retinoic acid responsiveness was also investigated in NCI-H1792, which, despite expressing endogenous RAR-beta, was found to be resistant to growth inhibition by all-trans-retinoic acid; transfection of exogenous RXR-alpha and RAR-alpha partially restored responsiveness, whereas RAR-beta was ineffective [21].

Large-Scale Genomic and Proteomic Resources

NCI-H1792 is one of the most thoroughly characterised NSCLC lines in public databases. The CCLE project included NCI-H1792 in its foundational analysis of 947 cancer cell lines, pairing gene expression and copy number data with pharmacological profiles for 24 anticancer drugs across 479 of those lines to identify genetic predictors of drug sensitivity [22]. Subsequent expansion of the CCLE added RNA splicing, DNA methylation, histone modification, and microRNA expression layers for 1,072 lines including NCI-H1792, providing an integrated multi-omics framework for drug-response prediction [23].

Proteomic characterisation has been conducted at multiple levels. Reverse-phase protein array (RPPA) analysis quantified approximately 230 cancer-related proteins across more than 650 cancer cell lines, with NCI-H1792 among the lines profiled, demonstrating that phosphoproteomic data predict drug sensitivity beyond what RNA alone can provide [24]. Mass spectrometry-based quantitative proteomics of the CCLE panel further expanded this dataset to thousands of proteins across 375 cell lines [25], and a pan-cancer proteomic map of 949 lines incorporating CRISPR-Cas9 essentiality data identified protein biomarkers of cancer vulnerabilities beyond the transcriptomic level [26].

Phosphoproteomic surveys of NSCLC also featured NCI-H1792. Rikova et al. profiled tyrosine kinase activity across 41 NSCLC cell lines and over 150 tumours, identifying activated kinases including EGFR, c-Met, ALK and ROS fusion proteins, PDGFR-alpha, and DDR1 in specific line subsets [27]. A multi-omics reconstruction of KRAS-dependent signalling networks used NCI-H1792 in a panel integrating transcriptome, proteome, and phosphoproteome data to identify three therapeutic sub-networks, centred on KRAS and MET, on LCK and PAK1, and on β-catenin [28]. Byers et al. employed an integrative proteomic and transcriptomic comparison of SCLC and NSCLC lines, with NCI-H1792 contributing to the NSCLC reference dataset revealing elevated E2F1-regulated factors and PARP1 in SCLC [29].

Conclusion

NCI-H1792 is a molecularly defined, multi-omics-annotated lung adenocarcinoma model that combines an oncogenic KRAS G12C mutation with wild-type LKB1 expression and a homozygous TP53 splice-donor mutation. Its inclusion in the CCLE, the NCI RAS mutant KRAS panel, and the Cancer Dependency Map provides an unparalleled reference framework for contextualising experimental results. Studies in NCI-H1792 have advanced understanding of KRAS effector engagement, resistance to MEK inhibitors acting on the RAF–MEK–ERK pathway, LKB1–AMPK–mTOR signalling, apoptosis regulation, and chemotherapy resistance, making it valuable for both mechanistic and translational NSCLC research. Whether you are investigating KRAS-targeted therapies, mapping apoptotic signalling, or building 3D tumour microenvironment models, NCI-H1792 offers a robust and well-validated experimental platform. Explore the full specifications or order NCI-H1792 Cells at cytion.com.

Key Publications

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17. Raungrut P, Tanyapattrapong S, Masjon T (2024) Transcriptomic Profiling of Carboplatin- and Paclitaxel-Resistant Lung Adenocarcinoma Cells Reveals CSF3 as a Potential Biomarker for the Carboplatin Plus Paclitaxel Doublet Regimens. Current issues in molecular biology. PMID: 39727962
18. Geater SL, Chaniad P, Trakunram K (2022) Diagnostic and prognostic value of serum miR-145 and vascular endothelial growth factor in non-small cell lung cancer. Oncology letters. PMID: 34820011
19. Okada J, Yamada E, Saito T (2020) Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity. Molecules (Basel, Switzerland). PMID: 31979355
20. Jiang F, Caraway NP, Li R (2005) RNA silencing of S-phase kinase-interacting protein 2 inhibits proliferation and centrosome amplification in lung cancer cells. Oncogene. PMID: 15735730
21. Wan H, Hong WK, Lotan R (2001) Increased retinoic acid responsiveness in lung carcinoma cells that are nonresponsive despite the presence of endogenous retinoic acid receptor (RAR) beta by expression of exogenous retinoid receptors. Cancer research. PMID: 11212249
22. Barretina J, Caponigro G, Stransky N (2012) The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. PMID: 22460905
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