Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib

Gautschi, Oliver; Peters, Solange; Zoete, Vincent; Aebersold-Keller, Franziska; Strobel, Klaus; Schwizer, Bernhard; Hirschmann, Astrid; Michielin, Olivier; Diebold, Joachim

doi:10.1016/j.lungcan.2013.08.012

Cited by 31 publications

(16 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preclinical studies suggest that classifying BRAF mutants by underlying kinase activity and RAF signaling mechanism may be more informative than grouping tumors according to V600 status (14,16,21). These preclinical observations are supported by case reports and small series demonstrating distinct activity of available BRAF inhibitors in lung cancers with class I, II, or III mutations (19,22,23). Here, we present the largest clinical cohort of patients with BRAF-mutant NSCLC to date.…”

Section: Discussionmentioning

confidence: 74%

Impact of BRAF Mutation Class on Disease Characteristics and Clinical Outcomes in BRAF-mutant Lung Cancer

Dagogo‐Jack

Martı́nez

Yeap

et al. 2019

Clinical Cancer Research

View full text Add to dashboard Cite

mutations are divided into functional classes distinguished by signaling mechanism and kinase activity: V600-mutant kinase-activating monomers (class I), kinase-activating dimers (class II), and kinase-inactivating heterodimers (class III). The relationship between functional class and disease characteristics in BRAF-mutant non-small cell lung cancer (NSCLC) has not been fully explored. We performed a retrospective analysis of BRAF-mutant NSCLCs treated at 2 institutions from 2005 to 2017 to determine clinicopathologic characteristics, progression-free survival (PFS) on chemotherapy, and overall survival (OS). We identified 236 patients with BRAF-mutant NSCLC ( = 107 class I, = 75 class II, and = 54 class III). Patients with class II or III mutations were more likely to have brain metastases ( ≤ 0.01) and coalterations ( ≤ 0.001) than class I. Compared with class I, PFS on chemotherapy was shorter for class II ( = 0.069) and class III ( = 0.034). OS was shorter for class II and III (class I, 40.1 months; class II, 13.9 months; and class III, 15.6 months; I vs. II, < 0.001; I vs. III, = 0.023); however, this difference was driven by fewer extrathoracic metastases and higher use of targeted therapies in class I patients. When patients treated with targeted therapy and those with thoracic-only metastases were excluded, there was no difference in OS across the 3 classes. BRAF-mutant NSCLC is a heterogeneous disease that encompasses 3 distinct functional classes. Classes II and III have more aggressive clinical features leading to less favorable outcomes. The distinct biological characteristics of class II and III tumors suggest that class-specific therapies may be necessary to effectively target these molecular subsets.

show abstract

Section: Discussionmentioning

confidence: 74%

Impact of BRAF Mutation Class on Disease Characteristics and Clinical Outcomes in BRAF-mutant Lung Cancer

Dagogo‐Jack

Martı́nez

Yeap

et al. 2019

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…While response rates in this sub-population are impressive, approximately half do not respond, and the majority of the responders will eventually acquire resistance [10] . Many genetic mechanisms of resistance have been cataloged [11] , including NF1 loss-of-function mutations [12] , NRAS activating mutations, BRAFV600E splicing variant, MEK1 mutation, COT expression, BRAFV600E amplification, BRAF G469L mutation [13] , concurrent MEK2 mutation and BRAF amplification [14] , AEBP1 upregulation [15] , MAP2K2 and MITF genomic alterations [16] and MEK2 Q60P mutation [17] , all of which result in reactivation of MAPK signaling, as well as the activation of parallel survival pathways such IGF1R/PI3K-AKT signaling [18] .…”

Section: V600 Point Mutations In Melanomamentioning

confidence: 99%

Many are better than one - Next Generation Multi-Variate Biomarkers for Precision Oncology

Kirouac²,

Schoeberl

2017

Can Cell Microenviron

View full text Add to dashboard Cite

Existing companion diagnostics have helped to match drug treatments to patients. However, they are largely restricted to single-molecule, single-time-point measurements, which cannot capture the full dynamic complexity of cancer biology. The development of multivariate and even dynamic biomarkers for diagnostic assays could allow more patients to benefit from improved drug regimens. Here we describe our work which provides a case study of multivariate biomarkers where we integrated experimental data generated using multivariate profiling technologies with a variety of computational modeling and simulation methods to identify such biomarkers and make clinical predictions on their therapeutic utility. We believe this approach of integrating multivariate profiling technologies and computational models, and iterating between experimental discovery and model predictions, will be required to develop the next generation of multivariate diagnostics and realize the promise of precision medicine.

show abstract

“…D594A, G466V) that nonetheless still retain oncogenic activity either through transactivating the catalytically competent RAS or CRAF by facilitating dimerization or through abrogation of autoinhibition thus leading to constitutive kinase activity 19 . Due to the low frequency of these mutations, efficacy of firstgeneration BRAF mutant selective inhibitors is mostly characterized in preclinical models with non-V600 mutants (e.g.…”

Section: Rafmentioning

confidence: 99%

Alterations in genes other than <i>EGFR/ALK/ROS1</i> in non-small cell lung cancer: trials and treatment options

Desai¹,

Menon²,

Dy³

2016

Cancer Biology &Amp; Medicine

View full text Add to dashboard Cite

During the last decade, we have seen tremendous progress in the therapy of lung cancer. Discovery of actionable mutations in EGFR and translocations in ALK and ROS1 have identified subsets of patients with excellent tumor response to oral targeted agents with manageable side effects. In this review, we highlight treatment options including corresponding clinical trials for oncogenic alterations affecting the receptor tyrosine kinases MET, FGFR, NTRK, RET, HER2, HER3, and HER4 as well as components of the RAS-RAF-MEK signaling pathway.

show abstract

Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib

Cited by 31 publications

References 17 publications

Impact of BRAF Mutation Class on Disease Characteristics and Clinical Outcomes in BRAF-mutant Lung Cancer

Impact of BRAF Mutation Class on Disease Characteristics and Clinical Outcomes in BRAF-mutant Lung Cancer

Many are better than one - Next Generation Multi-Variate Biomarkers for Precision Oncology

Alterations in genes other than <i>EGFR/ALK/ROS1</i> in non-small cell lung cancer: trials and treatment options

Contact Info

Product

Resources

About