Abstract PR-2: KRAS mutation and amplification status predicts sensitivity to antifolate therapies in non-small cell lung cancer.

2011 ◽  
Author(s):  
Sarah Bacus
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Melatonin Downregulates PD-L1 Expression and Modulates Tumor Immunity in KRAS-Mutant Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5649
Author(s):  
Yi-Chun Chao ◽  
Kang-Yun Lee ◽  
Sheng-Ming Wu ◽  
Deng-Yu Kuo ◽  
Pei-Wei Shueng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Tumor Immunity ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Syngeneic Mouse Model

Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.

Characterization of KRAS Mutation Subtypes in Non-Small Cell Lung Cancer

2021 ◽  
pp. molcanther.0201.2021
Author(s):  
Julia Judd ◽  
Nagla Abdel Karim ◽  
Hina Khan ◽  
Abdul Rafeh Naqash ◽  
Yasmine Baca ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Early assessment of KRAS mutation in cfDNA correlates with risk of progression and death in advanced non-small-cell lung cancer

2020 ◽  
Vol 123 (1) ◽  
pp. 81-91 ◽  
Author(s):  
Elisabetta Zulato ◽  
Ilaria Attili ◽  
Alberto Pavan ◽  
Giorgia Nardo ◽  
Paola Del Bianco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Assessment ◽  
Risk Of Progression

scholarly journals Cytology Samples (S) for EGFR and KRAS Mutation (MUT) Testing in Non-Small-Cell Lung Cancer (NSCLC). Experience from a Single Institution

2012 ◽  
Vol 23 ◽  
pp. ix431-ix432
Author(s):  
T. Moran Bueno ◽  
E. Castella Fernandez ◽  
M. Tierno Garcia ◽  
C. Buges Sanchez ◽  
C. Queralt Herrero ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Institution

scholarly journals Optimised Pre-Analytical Methods Improve KRAS Mutation Detection in Circulating Tumour DNA (ctDNA) from Patients with Non-Small Cell Lung Cancer (NSCLC)

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0150197 ◽  
Author(s):  
James L. Sherwood ◽  
Claire Corcoran ◽  
Helen Brown ◽  
Alan D. Sharpe ◽  
Milena Musilova ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Analytical Methods ◽  
Kras Mutation ◽  
Mutation Detection ◽  
Small Cell ◽  
Small Cell Lung ◽  
Circulating Tumour Dna

scholarly journals Response rate of patients with baseline brain metastases from recently diagnosed non‐small cell lung cancer receiving radiotherapy according to EGFR , ALK and KRAS mutation status

2020 ◽  
Vol 11 (4) ◽  
pp. 1026-1037 ◽  
Author(s):  
Oscar Arrieta ◽  
Laura‐Alejandra Ramírez‐Tirado ◽  
Enrique Caballé‐Perez ◽  
Alberto Mejia‐Perez ◽  
Zyanya Lucia Zatarain‐Barrón ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Response Rate ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Kras Mutation Status

Significance of EGFR and KRAS gene mutation in small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18564-e18564 ◽  
Author(s):  
Koji Kurokawa ◽  
Tomoharu Matsui ◽  
Hideko Ikeda ◽  
Shingo Nishikawa ◽  
Takashi Sone ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Lung Tumor ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung

e18564 Background: In non-small cell lung cancer, epidermal growth factor receptor (EGFR) and KRAS are known as driver mutations. However the association between these gene alteration and small cell lung cancer (SCLC) has been unclear. The aim of this study is to investigate the gene status of EGFR and Kras in SCLC. Methods: This retrospective study included 66 SCLC patients with available tumor tissue from primary lung tumor or metastatic and clinical data including survival. We evaluated for the presence of EGFR and KRAS mutation those patients using Scorpion-ARMS method. This study was approved by IRB. Results: Sixty-six patients (52 male,14 female median age 68 range 49-89, LD/ED 34/32, PS0-1/2-3 57/9, smoker/never smoker 64/2) were evaluated. Their median overall survival (OS) were 484 days, progression-free survival (PFS) were 217 days. Sixty-six samples were evaluated EGFR mutation test and 61 were evaluated KRAS mutation test by Scorpion-ARMs methods. SCLC patients with EGFR mutation were the only one patients (1.5%,1/66). KRAS mutation were also the only one patients (1.6%,1/61). A 54 years-old nevere-smoker female was already treated with EGFR tyrosine kinase inhibitor for non-small cell lung cancer, the patients with EGFR mutation had a transformation into SCLC. The KRAS mutation patient was combined SCLC with adenocarcinoma. Conclusions: This study suggested that EGFR and KRAS patients associated with SCLC is poor, these driver mutation is unnecessary for common SCLC.

Therapeutic impact of mutation subtypes and concomitant STK11 mutations in KRAS–mutated non-small cell lung cancer (NSCLC): A result of nationwide genomic screening project (LC-SCRUM-Japan).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9589-9589 ◽  
Author(s):  
Yutaro Tamiya ◽  
Yoshitaka Zenke ◽  
Shingo Matsumoto ◽  
Naoki Furuya ◽  
Tomohiro Sakamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Genomic Screening

9589 Background: KRAS mutations are one of the common oncogene drivers in non-small cell lung cancer (NSCLC), and the development of several targeted drugs for KRAS-mutated NSCLC is now ongoing. However, the clinical impact of KRAS mutation subtypes or concomitant other gene mutations in NSCLC patients (pts) remains unclear. Methods: In a nationwide genomic screening project (LC-SCRUM-Japan), we have prospectively analyzed lung cancer pts for genetic alterations and tumor mutation burden (TMB) by next-generation sequencing system, and for PD-L1 expression by immunohistochemistry (22C3 antibody). The therapeutic efficacy and survival of KRAS-mutated non-squamous (non-sq) NSCLC pts were evaluated using a clinico-genomic database of the LC-SCRUM-Japan. Results: A total of 5166 non-sq NSCLC pts enrolled from 2015 to 2019. KRAS mutations were detected in 794 pts (15%; G12C/G12D/G12V/G12A/G13X/others = 232/186/165/66/61/84). Among the 794 pts, TMB and PD-L1 expression were analyzed in 128 and 79, respectively, and 218 received PD-1/PD-L1 inhibitors (IO) after 1st-line chemotherapy. The median age was 66 years (range, 29-89). 142 pts (65%) were male and 172 (78%) were smokers. Concomitant STK11 mutations were detected in 33 pts (15%) with no difference in the mutation frequency among KRAS mutation subtypes. KRAS G12C was significantly associated with high TMB (≥ 10 mut/Mb) (p = 0.03), and KRAS G12C or G12V with high PD-L1 expression (≥ 50%) (p = 0.02). In pts who received IO, median progression-free survival (mPFS) was significantly longer in pts with KRAS G12C or G12V than in those with other KRAS mutations (4.7 vs 2.0 months, hazard ratio (HR) 0.58 [95%CI 0.43-0.78], p < 0.01). Among pts with KRAS G12C or G12V, mPFS of IO was significantly shorter in pts with concomitant STK11 mutations than in those without (1.8 vs. 5.7 months, HR 1.97 [95%CI 1.06-3.41], p = 0.02). These correlations were not observed in platinum-containing chemotherapy (Plt-CTx). There were also no significant differences in IO and Plt-CTx efficacies between with and without other concomitant mutations, such as TP53, RB1, CDKN2A and PTEN mutations. Conclusions: Non-sq NSCLC pts with KRAS G12C/V were more sensitive to IO therapies than those with other KRAS mutations, but KRAS G12C/V-positive pts with concomitant STK11 mutations were less sensitive than those without. These results could be highly informative in the development of novel targeted therapies for KRAS-mutated NSCLC.

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