Genomic Landscape, Clinical Features and Outcomes of Non-Small Cell Lung Cancer Patients Harboring BRAF Alterations of Distinct Functional Classes

Federico, Alessandro Di; Giglio, Andrea De; Gelsomino, Francesco; Biase, Dario de; Giunchi, Francesca; Palladini, Arianna; Sperandi, Francesca; Melotti, Barbara; Ardizzoni, Andrea

doi:10.3390/cancers14143472

Cited by 7 publications

(4 citation statements)

References 80 publications

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“…Smoking history can be associated with BRAF mutations, as well as KRAS, MET , and other mutations 9 , 28 , 29 . However, a few studies have also suggested that BRAF V600E is less associated with smoking history than other BRAF mutations 26 , 30 , 31 . Therefore, all patients with advanced NSCLC regardless of smoking history should undergo broad-based mutation testing, including BRAF 5 , 21 , 22 .…”

Section: Braf-mutant Metastatic Nsclc Disease Overviewmentioning

confidence: 99%

BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

Planchard,

Sanborn,

Negrao

et al. 2024

npj Precis. Onc.

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In this review, we cover the current understanding of BRAF mutations and associated clinical characteristics in patients with metastatic NSCLC, approved and emerging treatment options, BRAF sequencing approaches, and unmet needs. The BRAFV600E mutation confers constitutive activity of the MAPK pathway, leading to enhanced growth, proliferation, and survival of tumor cells. Testing for BRAF mutations enables patients to be treated with therapies that directly target BRAFV600E and the MAPK pathway, but BRAF testing lags behind other oncogene testing in metastatic NSCLC. Additional therapies targeting BRAFV600E mutations provide options for patients with metastatic NSCLC. Emerging therapies and combinations under investigation could potentially overcome issues of resistance and target non-V600E mutations. Therefore, because targeted therapies with enhanced efficacy are on the horizon, being able to identify BRAF mutations in metastatic NSCLC may become even more important.

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Section: Braf-mutant Metastatic Nsclc Disease Overviewmentioning

confidence: 99%

BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

Planchard,

Sanborn,

Negrao

et al. 2024

npj Precis. Onc.

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“…Recently, an analysis of patients ( n =35) carrying non-V600 mutations enrolled in the POPLAR and OAK phase II and phase III trials on second-line atezolizumab 85 , 86 reported shorter OS than that of patients with wild-type BRAF (8.4 versus 11.5 months; HR 1.70 (95% CI 1.19–2.44); p =0.0033). 87 …”

Section: Reviewmentioning

confidence: 99%

“… 78 Similarly, in a cohort of 139 patients with BRAF -mutant NSCLC, median TMB was significantly higher in class 3 than in the other classes ( p <0.001). 87 …”

Section: Reviewmentioning

confidence: 99%

Non-small-cell lung cancer: how to manage BRAF-mutated disease

Guaitoli¹,

Zullo²,

Tiseo³

et al. 2023

DIC

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BRAF mutations are reported in about 3–5% of non-small-cell lung cancer (NSCLC), almost exclusively in adenocarcinoma histology, and are classified into three different classes. The segmentation of BRAF mutations into V600 (class 1) and non-V600 (classes 2 and 3) relies on their biological characteristics and is of interest for predicting the therapeutic benefit of targeted therapies and immunotherapy. Given the relative rarity of this molecular subset of disease, evidence supporting treatment choices is limited. This review aims to offer a comprehensive update about available therapeutic options for patients with NSCLC harbouring BRAF mutations to guide the physician in the choice of treatment strategies. We collected the most relevant available data, from single-arm phase II studies and retrospective analyses conducted in advanced NSCLC, regarding the efficacy of BRAF and MEK inhibitors in both V600 and non-V600 BRAF mutations. We included case reports and smaller experiences that could provide information on specific alterations. With respect to immunotherapy, we reviewed retrospective evidence on immune-checkpoint inhibitors in this molecular subset, whereas data about chemo-immunotherapy in this molecular subgroup are lacking. Moreover, we included the available, though limited, retrospective evidence of immunotherapy as consolidation after chemo-radiation for unresectable stage III BRAF -mutant NSCLC, and an overview of ongoing clinical trials in the peri-operative setting that could open new perspectives in the future.

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“…On the contrary, substitutions present in other codons of BRAF genes do not seem to have the oncogenic potential [ 7 , 9 ]. According to their activity, BRAF mutations have been classified into three functional classes [ 9 , 12 , 13 ]: (i) class 1 BRAF mutations (BRAF p.V600), RAS independent, signal as monomers, and characterized by strong activity of BRAF kinase domain; (ii) class 2 BRAF alterations, RAS independent, signal as constitutive dimers, and with intermediate to high activity of BRAF kinase domain; (iii) class 3 BRAF alterations, RAS dependent, characterized by low or absent kinase activity.…”

Section: Introductionmentioning

confidence: 99%

Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre

Leo

Şerban

Maloberti

et al. 2023

IJMS

Self Cite

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The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.

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Genomic Landscape, Clinical Features and Outcomes of Non-Small Cell Lung Cancer Patients Harboring BRAF Alterations of Distinct Functional Classes

Cited by 7 publications

References 80 publications

BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

Non-small-cell lung cancer: how to manage BRAF-mutated disease

Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre

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