EGFR and KRAS mutations in lung carcinomas in the Dutch population: increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma

Smits, Alexander J.; Kummer, J. Alain; Hinrichs, John W. J.; Herder, Gerarda J.M.; Scheidel-Jacobse, Karen C.; Jiwa, Natasha; Ruijter, T. Emiel G.; Nooijen, Peet; Looijen-Salamon, Monika; Ligtenberg, Marjolijn J. L.; Thunnissen, Erik; Heideman, Daniëlle A.M.; Weger, Roel A. de; Vink, Aryan

doi:10.1007/s13402-012-0078-4

Cited by 100 publications

(87 citation statements)

References 31 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In lung adenocarcinoma, KRAS mutations are more common in smokers (12)(13)(14)(15)(16). The prognostic significance of KRAS mutations in NSCLC is controversial (17)(18)(19). Maitra et al (20) identified KRAS mutations in 2 (17%) of 12 gallbladder EPSCC patients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer

et al. 2016

View full text Add to dashboard Cite

Background: Lung cancer is one of the most lethal cancers. It is mainly classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6% of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have several similar features but their clinical course is different. Aims: We investigated the KRAS mutation status in SCLC and EPSCC. Study design: Mutation research. Methods: Thirty-seven SCLC and 15 EPSCC patients were included in the study. The pathological diagnoses were confirmed by a second pathologist. KRAS analysis was performed in our medical genetic department. DNA isolation was performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen; Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen; Hilden, Germany) was used for KRAS analyses. Results: Thirty-four (91.9%) of the SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female. SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R (CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS mutant and wild type patients were compared in the SCLC group, no difference was found for overall survival (p=0.6). Conclusion: In previous studies, the incidence of KRAS mutation in SCLC was 1-3%; however, it was 16.2% in our study. Therefore, there may be ethnic and geographical differences in the KRAS mutations of SCLC. As a result, KRAS mutation should not be excluded in SCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In our study, 6 (16.2%) of 37 SCLC patients had KRAS mutations. There were ethnic and geographical differences in the KRAS mutation status of patients with colorectal cancer and NSCLC (19,23,24). Genetic, dietary and environmental factors play a role in the development of KRAS mutations.…”

Section: Discussionmentioning

confidence: 99%

KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…A typical tumor contains two to eight driver mutations that can affect as many as 12 key cellular signaling pathways. Reported genetic alterations for lung adenocarcinoma include: EGFR (32,(42)(43)(44)(45)(46)(47), KRAS (42,(48)(49)(50)(51)(52), BRAF (53)(54)(55)(56), and ERBB2 (formerly HER2) (45, 56-60) driver mutations; ROS1 (32,(61)(62)(63), KIF5b-RET (32,64,65), and EML4-ALK rearrangements (20,45,57,61,(66)(67)(68)(69)(70); and other gene amplifications (20). An estimated 50% of lung adenocarcinomas in patients in Western populations have either an EGFR or KRAS driver mutation (42).…”

Section: Clinical Issuesmentioning

confidence: 99%

“…An estimated 50% of lung adenocarcinomas in patients in Western populations have either an EGFR or KRAS driver mutation (42). The two mutations are mutually exclusive (52). In approximately 30-40% of patients with adeno-carcinoma a driver mutation has not been identified (20), which leaves substantial room for the development of additional targeted treatments for these tumors.…”

Section: Clinical Issuesmentioning

confidence: 99%

“…Such statements appear to be based on early trials of EGFR mutations and tyrosine kinase inhibitor treatment that seemed to indicate that these mutations occurred almost exclusively in never-smokers (47,(71)(72)(73), while KRAS mutations are more common in current and former smokers. Smoking status is not, however, the important distinguishing factor in these cases, as EGFR and KRAS mutations commonly occur in both smokers (42,48,77) and nonsmokers and are at the same time mutually exclusive (52). The key distinction is that EGFR mutations, even when identified in current or former smokers, are not caused by smoking (20,87), while two different KRAS mutations -one associated with smoking, the other not associated with smoking -have been identified in the published literature.…”

Section: Lung Cancer In a Smoker Is Not Inherently Different From Lunmentioning

confidence: 99%

See 1 more Smart Citation

Implications of Evolving Medical Science for Proof of Lung Cancer Causation

Frarey¹,

Martínez²

2015

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

View full text Add to dashboard Cite

SummaryCausal determination in cases of diseases involving multiple risk factors and long development time poses formidable challenges to judges and juries. Numerous scientific, medical and legal questions are involved. For example, is the mere presence of a factor known to be associated with elevated disease risk sufficient for a causal determination? If not, what level of exposure should be deemed sufficient, and how can that exposure be measured with adequate confidence over an extended period? In the presence of two or more factors associated with elevated disease risk, how can causation be demonstrated and apportioned among these factors, particularly when the potential effects of their interaction are unknown? With increasing knowledge of the molecular and genetic changes involved in disease development, what level of comprehension and proof is sufficient to implicate a specific risk factor in the complex causal mechanism of an individual’s disease? Lung cancer, notwithstanding its strong association with cigarette smoking, represents a group of diseases associated with both a variety of risk factors and relatively long development time. Both the published scientific literature and current clinical practice for the treatment of lung cancer, particularly lung adenocarcinoma, reflect the rapid changes that have occurred in this field over the past decade. These medical advances, in addition to promising better prognosis for some lung cancer patients, have implications for the proof of lung cancer causation in litigation in which plaintiffs contend that tobacco smoke exposure caused their disease. This is particularly true in cases arising in many European countries and other jurisdictions in which little or no histological or cytological information has been produced by plaintiffs. This paper examines the rapidly evolving science underpinning lung cancer diagnosis and treatment and its forensic implications. [Beitr. Tabakforsch. Int. 26 (2015) 298-311]

show abstract

Mutant‐Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug‐Resistant Mutations

Jang

Clercq

et al. 2020

Angewandte Chemie

View full text Add to dashboard Cite

Targeting epidermal growth factor receptor (EGFR) through an allosteric mechanism provides a potential therapeutic strategy to overcome drug‐resistant EGFR mutations that emerge within the ATP binding site. Here, we develop an allosteric EGFR degrader, DDC‐01‐163, which can selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells while leaving wildtype EGFR Ba/F3 cells unaffected. DDC‐01‐163 is also effective against osimertinib‐resistant cells with L/T/C797S and L/T/L718Q EGFR mutations. When combined with an ATP‐site EGFR inhibitor, osimertinib, the anti‐proliferative activity of DDC‐01‐163 against L858R/T790M EGFR‐Ba/F3 cells is enhanced. Collectively, DDC‐01‐163 is a promising allosteric EGFR degrader with selective activity against various clinically relevant EGFR mutants as a single agent and when combined with an ATP‐site inhibitor. Our data suggests that targeted protein degradation is a promising drug development approach for mutant EGFR.

show abstract

EGFR and KRAS mutations in lung carcinomas in the Dutch population: increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma

Cited by 100 publications

References 31 publications

KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer

KRAS Mutation in Small Cell Lung Carcinoma and Extrapulmonary Small Cell Cancer

Implications of Evolving Medical Science for Proof of Lung Cancer Causation

Mutant‐Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug‐Resistant Mutations

Contact Info

Product

Resources

About