Characterization of distinct types of KRAS mutation and its impact on first‑line platinum‑based chemotherapy in Chinese patients with advanced non‑small cell lung cancer

Jia, Yijun; Jiang, Tao; Li, Xuefei; Zhao, Chao; Zhang, Limin; Zhao, Sha; Liu, Xiaozhen; Qiao, Meng; Luo, Jiawei; Shi, Jinpeng; Yang, Hui; Wang, Yan; Liu, Xi; Zhang, Shijia; Gao, Guanghui; Su, Chunxia; Ren, Shengxiang; Zhou, Caicun

doi:10.3892/ol.2017.7016

Cited by 35 publications

(54 citation statements)

References 45 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies on PFS of KRAS -mutated lung ADCA, irrespective of mode of treatment, also contradict each other. 20,41–44 PFS of KRAS wild type and mutated patients in our study differed marginally.…”

Section: Discussioncontrasting

confidence: 65%

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

Singh

Guleria

Malik

et al. 2019

Current Problems in Cancer

View full text Add to dashboard Cite

Mitogen-Activated Protein (MAP) Kinase pathway involves several oncogenic genes which can serve as potential targets for therapy. Therefore, aim of the present study is to analyze mutations in the MAP Kinase pathway in pulmonary adenocarcinoma (ADCA) of Indian patients along with clinico-pathologic correlation and determination of the survival status in patients receiving therapy. Blocks and slides of 125 pulmonary ADCA of last 5 years were retrieved. Histo-morphology and tumor content were determined. EGFR, KRAS, BRAF and MEK1 genes were analyzed using Sanger sequencing and Real-time polymerase chain reaction (PCR). Clinico-pathologic correlation and survival analysis were performed. Fifty-eight (46.4%) patients harbored genetic mutations of which 49 had single somatic mutations, 5 had multiple exonic and 4 showed coexisting EGFR and KRAS mutations. EGFR mutations were seen in 24.8%, KRAS in 19.2% and BRAF (non-V600E) in 2.4% cases. There was no difference in progression-free survival of wild- type/single mutations when compared with multiple/ coexisting mutations (P = 0.09). However, the P value may indicate borderline correlation. To conclude, EGFR and KRAS mutations may coexist in the same patient in lung ADCA. Multiple exonic mutations of KRAS gene formed substantial percentage of our cohort, requiring further exploration. Lung ADCA harbouring BRAF mutations are commonly non-V600E. Testing of all major genetic driver mutations of lung ADCA irrespective of histology and other demographic characteristics is necessary.

show abstract

Section: Discussioncontrasting

confidence: 65%

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

Singh

Guleria

Malik

et al. 2019

Current Problems in Cancer

View full text Add to dashboard Cite

show abstract

“…Patients harboring G12C mutation are more likely to present bone metastases dissemination, while pleuro-pericardial metastases are more frequent in those with G12V mutations. However, KRAS G12D mutations preferably activate PI3K and MEK signaling [ 51 , 52 ]. Furthermore, concurrent mutations of tumor suppressor genes in KRAS -mutant adenocarcinoma patients (e.g.…”

Section: Kras Biologymentioning

confidence: 99%

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

et al. 2018

View full text Add to dashboard Cite

Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed. Moreover, the role of KRAS oncogene in NSCLC remains unclear and its predictive and prognostic impact remains controversial. The study of the underlying biology of KRAS in NSCLC patients could help to determine potential candidates to evaluate novel targeted agents and combinations that may allow a tailored treatment for these patients. The aim of this review is to update the current knowledge about KRAS-mutated lung adenocarcinoma, including a historical overview, the biology of the molecular pathways involved, the clinical relevance of KRAS mutations as a prognostic and predictive marker and the potential therapeutic approaches for a personalized treatment of KRAS-mutated NSCLC patients.

show abstract

“…Point mutations in the KRAS gene are present in approximately 35-45% of colorectal cancers (Dinu et al 2014;Tan and Du 2012), and serve as a negative predictive factor of response to anti-EGFR therapy (Lievre et al 2006). These mutations lead to the loss of intrinsic GTPase activity and therefore to increased proliferation and resistance to apoptosis (Jia et al 2017). The majority of KRAS mutations occur in codons 12 and 13, while other mutations, such as those in codons 61 and 146 are less common (Guarnaccia et al 2018;Margonis et al 2015;Stolze et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Metabolic characterization of colorectal cancer cells harbouring different KRAS mutations in codon 12, 13, 61 and 146 using human SW48 isogenic cell lines

Varshavi

McCarthy

et al. 2020

Metabolomics

View full text Add to dashboard Cite

Introduction Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutations occur in approximately one-third of colorectal (CRC) tumours and have been associated with poor prognosis and resistance to some therapeutics. In addition to the well-documented pro-tumorigenic role of mutant Ras alleles, there is some evidence suggesting that not all KRAS mutations are equal and the position and type of amino acid substitutions regulate biochemical activity and transforming capacity of KRAS mutations. Objectives To investigate the metabolic signatures associated with different KRAS mutations in codons 12, 13, 61 and 146 and to determine what metabolic pathways are affected by different KRAS mutations. Methods We applied an NMR-based metabonomics approach to compare the metabolic profiles of the intracellular extracts and the extracellular media from isogenic human SW48 CRC cell lines with different KRAS mutations in codons 12 (G12D, G12A, G12C, G12S, G12R, G12V), 13 (G13D), 61 (Q61H) and 146 (A146T) with their wild-type counterpart. We used false discovery rate (FDR)-corrected analysis of variance (ANOVA) to determine metabolites that were statistically significantly different in concentration between the different mutants. Results CRC cells carrying distinct KRAS mutations exhibited differential metabolic remodelling, including differences in glycolysis, glutamine utilization and in amino acid, nucleotide and hexosamine metabolism. Conclusions Metabolic differences among different KRAS mutations might play a role in their different responses to anticancer treatments and hence could be exploited as novel metabolic vulnerabilities to develop more effective therapies against oncogenic KRAS.

show abstract

Characterization of distinct types of KRAS mutation and its impact on first‑line platinum‑based chemotherapy in Chinese patients with advanced non‑small cell lung cancer

Cited by 35 publications

References 45 publications

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

Metabolic characterization of colorectal cancer cells harbouring different KRAS mutations in codon 12, 13, 61 and 146 using human SW48 isogenic cell lines

Contact Info

Product

Resources

About