Abstract 3264
Background
A subgroup of MEK1 mutations in human tumors were recently described as RAF- and phosphorylation independent and as insensitive to currently clinically used allosteric MEK inhibitors. We established a novel cell line that carries a MEK1 mutation of this class (pGlu102_Lys104delinsGln) and tested a novel ATP competitive MEK inhibitor (MAP855) in this model. According to our knowledge this is the first patient derived cell line with this type of MEK mutation and the first spitzoid melanoma cell model.
Methods
PF130 cell line was established from the pleural effusion sample of a 37-year-old male patient with spitzoid melanoma. NGS was used for mutational analysis. Cells were treated either with allosteric MEK inhibitor selumetinib or with newly developed ATP competitive MEK inhibitor MAP855. We analyzed changes in cell number, cell cycle distribution and ERK activation after treatment in vitro. Furthermore, the in vivo tumorigenicity was tested by injecting the cells subcutaneously, intrapleurally or intravenously into female SCID mice.
Results
We found that ATP competitive MEK inhibitor MAP855 strongly decreased the viability of PF130 cells, while allosteric inhibitor selumetinib did not. Cell cycle analysis showed that MAP588 treatment could induce cell death in PF130 cells in a concentration dependent manner and slightly reduced the amount of cells in the S and the G2M phases. Furthermore, MAP855 was able to reduce ERK protein activation in PF130 cells effectively while selumetinib treatment had no effect. In vivo, intrapleurally injected cells established macroscopic tumors in the chest cavity after two months while intravenously and subcutaneously delivered cells showed limited growth.
Conclusions
We established a new cellular model of tumors with RAF- and phosphorylation independent MEK mutation. We found that recently developed ATP-competitive MEK inhibitor MAP855 is a potent inhibitor of these cells in vitro. The in vivo efficacy is currently under investigation. Furthermore, we describe here to the best of our knowledge the first patient derived spitzoid melanoma cell model to test both in vitro and in vivo novel therapeutic modalities.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Balazs Hegedus.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2171 - CCND1 Amplification Contributes to Immunosuppression in Head and Neck Squamous Cell Carcinoma and the Association with a Poor Response to Immune Checkpoint Inhibitors
Presenter: Chloe Huang
Session: Poster Display session 3
Resources:
Abstract
2624 - Efficacy of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer patients with sensitive genes mutation
Presenter: Hui-Juan Cui
Session: Poster Display session 3
Resources:
Abstract
3494 - Neutrophil to Lymphocyte Ratio (NLR) kinetics as predictors of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (NSCLC) patients treated with nivolumab (N).
Presenter: Audrey Simonaggio
Session: Poster Display session 3
Resources:
Abstract
3964 - Predictive markers of checkpoint inhibitor activity in adult metastatic solid tumours
Presenter: Alexandra Pender
Session: Poster Display session 3
Resources:
Abstract
3041 - Blood-based TMB (bTMB) correlates with tissue-based TMB (tTMB) in a multi-cancer Phase I IO Cohort
Presenter: Daniel Araujo
Session: Poster Display session 3
Resources:
Abstract
3910 - Analysis of Molecular Profile Complexities for Immunotherapy Decision Support
Presenter: Robert Dóczi
Session: Poster Display session 3
Resources:
Abstract
4836 - The Role of Tumor Neoantigens in the Differential Response to Immunotherapy (IO) in EGFR and BRAF Mutated Lung Cancers - Quantity or Quality?
Presenter: Katrina Case
Session: Poster Display session 3
Resources:
Abstract
1929 - Impact of previous corticosteroid (CS) exposure on efficacy of Programmed Cell Death-(Ligand) 1 blockade in patients with advanced Non-Small-Cell Lung Cancer (NSCLC): a single Center retrospective analysis
Presenter: Fabrizio Nelli
Session: Poster Display session 3
Resources:
Abstract
2601 - Comparison 18F-FDG-PET/CT criteria for prediction of therapy response and clinical outcome in patients with metastatic melanoma treated with Ipilimumab and PD-1 inhibitors
Presenter: Sabrina Vari
Session: Poster Display session 3
Resources:
Abstract
3628 - Predictive model for survival in advanced non-small-cell lung cancer (NSCLC) treated with frontline pembrolizumab
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 3
Resources:
Abstract