2,756 results match your criteria mutated braf

A Covalent Calmodulin Inhibitor as a Tool to Study Cellular Mechanisms of K-Ras-Driven Stemness.

Front Cell Dev Biol 2021 8;9:665673. Epub 2021 Jul 8.

Cancer Cell Biology and Drug Discovery Group, Department of Life Sciences and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Recently, the highly mutated oncoprotein K-Ras4B (hereafter K-Ras) was shown to drive cancer cell stemness in conjunction with calmodulin (CaM). We previously showed that the covalent CaM inhibitor ophiobolin A (OphA) can potently inhibit K-Ras stemness activity. However, OphA, a fungus-derived natural product, exhibits an unspecific, broad toxicity across all phyla. Read More

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Tumor response to EGFR/BRAF/MEK co-inhibition in a patient with EGFR mutated lung adenocarcinoma developing a BRAF mutation as an acquired resistance mechanism.

Lung Cancer 2021 Jul 21;159:42-44. Epub 2021 Jul 21.

Department of Pulmonology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 11, 1200 Brussels, Belgium; Université catholique de louvain, Institut de Recherche Expérimentale et Clinique (IREC)/Pôle de Pneumologie, Belgium. Electronic address:

EGFR-mutant adenocarcinomas represent 12% of unselected lung adenocarcinomas and 44% of never smoker adenocarcinomas in the Caucasian population. Activating mutations like exon19 deletion or exon21 Leu858Arg point mutations are predictive of tumor response to EGFR tyrosine kinase inhibitors. Unfortunately, acquired resistance inevitably occurs by the development of novel EGFR mutations, mutations in other genes, gene amplification, gene fusion or tumor transformation. Read More

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Genomic landscape and evolution of arm aneuploidy in lung adenocarcinoma.

Neoplasia 2021 Jul 21;23(9):870-878. Epub 2021 Jul 21.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

For lung adenocarcinoma, arm aneuploidy landscape among primary and metastatic sites, and among different driver and frequently mutated gene groups have not been previously studied. We collected the largest cohort of LUAD patients (n=3533) to date and analyzed the profiles of chromosome arm aneuploidy (CAA), and its association with different metastatic sites and mutated gene groups. Our results showed distant metastasis (bone, brain, liver) were characterized by high CAA burden and biased towards arm losses compared to regional metastasis (pleura, chest) and primary tumors. Read More

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Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era.

Int J Mol Sci 2021 Jul 19;22(14). Epub 2021 Jul 19.

Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, 71122 Foggia, Italy.

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Read More

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Immune checkpoint inhibitors in oncogene-addicted non-small cell lung cancer: a systematic review and meta-analysis.

Transl Lung Cancer Res 2021 Jun;10(6):2890-2916

Université Paris-Saclay, Institut Gustave Roussy, Inserm, Biomarqueurs Prédictifs et Nouvelles Stratégies Thérapeutiques en Oncologie, Villejuif, France.

Background: Treatment of oncogene-addicted non-small cell lung cancer (NSCLC) has been changed by the advent of tyrosine kinase inhibitors (TKIs). Albeit great benefits are achieved with target therapies, resistance invariably occurs and recourse to alternative treatments is unavoidable. Immune checkpoint inhibitors (ICIs) role and the best setting of immunotherapy administration in oncogene-driven NSCLC are matter of debate. Read More

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Tumor suppressor miR-193a-3p enhances efficacy of BRAF/MEK inhibitors in BRAF-mutated colorectal cancer.

Cancer Sci 2021 Jul 20. Epub 2021 Jul 20.

Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Miyagi, Japan.

Patients with BRAF-mutated colorectal cancer (CRC) have a poor prognosis despite recent therapeutic advances such as combination therapy with BRAF, MEK, and EGFR inhibitors. To identify microRNAs (miRNAs) that can improve the efficacy of the BRAF inhibitor dabrafenib (DAB) and the MEK inhibitor trametinib (TRA), we screened 240 miRNA in BRAF-mutated CRC cells and identified five candidate miRNAs. Overexpression of miR-193a-3p, one of the five screened miRNAs, in CRC cells inhibited cell proliferation by inducing apoptosis. Read More

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The WHO 2018 Classification of Cutaneous Melanocytic Neoplasms: Suggestions From Routine Practice.

Front Oncol 2021 2;11:675296. Epub 2021 Jul 2.

Department of Dermatology, 'Luigi Vanvitelli' University School of Medicine, Naples, Italy.

The "multidimensional" World Health Organization (WHO) classification 2018 of melanocytic tumors encompasses nine melanoma pathways (seven of which for cutaneous melanoma) according to a progression model in which morphologically intermediate melanocytic tumors are cosidered as simulators and/or precursors to melanoma. These "intermediates" can be subclassified into: i) a "classical" subgroup (superficial/thin compound: dysplastic nevus), which is placed within the morphologic and molecular progression spectrum of classical (Clark's and McGovern's) melanoma subtypes (superficial spreading and, possibly, nodular); and ii) a "non-classical" subgroup (thick compound/dermal: "melanocytomas") whose genetic pathways diverge from classical melanoma subtypes. Such a progression model is aimed at giving a conceptual framework for a histopathological classification; however, routine clinicopathological practice strongly suggests that most melanomas arise and that the vast majority of nevi are clinically stable or even involuting over time. Read More

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Intratumor morphologic and transcriptomic heterogeneity in BRAF-mutated metastatic colorectal adenocarcinomas.

ESMO Open 2021 Jul 13;6(4):100211. Epub 2021 Jul 13.

Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy; Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. Electronic address:

Background: Intratumor heterogeneity (ITH) is described as the presence of various clones within one tumor, each with their own unique features in terms of morphology, inflammation, genetics or transcriptomics. Heterogeneity provides the fuel for drug resistance; therefore, an accurate assessment of tumor heterogeneity is essential for the development of effective therapies. The purpose of this study was to dissect morphologic and molecular ITH in colorectal adenocarcinoma. Read More

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[Therapeutic Strategy for BRAF-Mutated Cancer].

Gan To Kagaku Ryoho 2021 Jul;48(7):861-865

Dept. of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University.

BRAF mutation is occurred in about 8% of human malignancy, including 40-60% in malignant melanoma, 50% in thyroid papillary cancer, 10% in colorectal cancer, and a few percent of non-small cell lung cancer. Activated mutation of BRAF is mainly p. V600E mutation. Read More

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BRAF testing in metastatic colorectal carcinoma and novel, chemotherapy-free therapeutic options.

Pathologe 2021 Jul 14. Epub 2021 Jul 14.

Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany.

In the past 25 years, treatment of metastatic colorectal cancer (mCRC) has undergone profound changes. The approval of newer chemotherapeutics such as irinotecan and oxaliplatin was followed in 2005 by the first targeted therapies, for example, monoclonal antibodies directed against the epidermal growth factor receptor (EGFR), as cetuximab and panitumumab, or the angiogenesis inhibitors bevacizumab, ramucirumab, and aflibercept. With the rapidly progressing molecular characterization of mCRC in the last 10 years and the classification of the disease in four consensus subtypes, further changes are emerging, which will promote, among other things, the introduction of protein-kinase inhibitors developed for specific molecular aberrations as well as immune checkpoint inhibitors into the treatment algorithm. Read More

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Plasma proteome alterations by MAPK inhibitors in BRAF-mutated metastatic cutaneous melanoma.

Neoplasia 2021 Aug 8;23(8):783-791. Epub 2021 Jul 8.

Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden.

Approximately half of metastatic cutaneous melanomas (CM) harbor a mutation in the BRAF protooncogene, upregulating the mitogen-activated protein kinase (MAPK)-pathway. The development of inhibitors targeting the MAPK pathway (MAPKi), i.e. Read More

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GJB5 association with BRAF mutation and survival in cutaneous malignant melanoma.

Br J Dermatol 2021 Jul 8. Epub 2021 Jul 8.

Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia, 13900, Biella, Italy.

Background: Gap junctional intercellular communication is crucial for epidermal cellular homeostasis. Inability to establish melanocyte-keratinocytes contacts and loss of intercellular junction's integrity may contribute to melanoma development. Connexins, laminins and desmocollins have been implicated in the control of melanoma growth, where their reduced expression has been reported in metastatic lesions. Read More

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A mutual information-based in vivo monitoring of adaptive response to targeted therapies in melanoma.

Neoplasia 2021 Aug 5;23(8):775-782. Epub 2021 Jul 5.

Dermato-Oncology Unit, Division of Dermatology, University Hospital of Geneva, Switzerland; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Switzerland. Electronic address:

The mechanisms of adaptive resistance to genetic-based targeted therapies of solid malignancies have been the subject of intense research. These studies hold great promise for finding co-targetable hub/pathways which in turn would control the downstream non-genetic mechanisms of adaptive resistance. Many such mechanisms have been described in the paradigmatic BRAF-mutated melanoma model of adaptive response to BRAF inhibition. Read More

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The Association Between Radioiodine Refractory in Papillary Thyroid Carcinoma, Sodium/Iodide Symporter Expression, and Mutation.

Onco Targets Ther 2021 29;14:3959-3969. Epub 2021 Jun 29.

Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.

Objective: To study the association between radioiodine refractory papillary thyroid carcinoma, sodium/iodide symporter (NIS) expression, and the mutation.

Methods: A study was conducted on 30 radioiodine refractory papillary thyroid carcinoma patients and 30 radioiodine-avid papillary thyroid carcinoma patients. The expressions of sodium/iodide symporter and mutated protein were determined by immunohistochemistry using formalin-fixed, paraffin-embedded tissue. Read More

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Effective treatment of a BRAF V600E-mutant epithelioid glioblastoma patient by vemurafenib: a case report.

Anticancer Drugs 2021 Jul 4. Epub 2021 Jul 4.

Department of Critical Care Medicine, Jiangxi Provincial People's Hospital, Nanchang Department of Neurosurgery, Nanfang Hospital, Southern Medical University Nanfang Glioma Center, Nanfang Hospital Southern Medical University, Guangdong, China.

Epithelioid glioblastoma (E-GBM) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of central nervous system tumors. About half of these tumors show the BRAF mutant. Therefore, this is a target of special interest for this group of patients. Read More

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Whole Tumor Capsule Is Prognostic of Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer.

J Clin Endocrinol Metab 2021 Jul 3. Epub 2021 Jul 3.

Department of Clinical and Experimental Medicine, Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy.

Context: Tumor capsule integrity is becoming a relevant issue to predict the biological behavior of human tumors, including thyroid cancer.

Objective: This work aims to verify whether a whole tumor capsule in the classical variant of papillary thyroid carcinoma (CVPTC) could have as a predictive role of a good outcome as for follicular variant (FVPTC).

Methods: FVPTC (n = 600) and CVPTC (n = 554) cases were analyzed. Read More

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Kinase Inhibitors in the Treatment of Thyroid Cancer: Institutional Experience.

Acta Clin Croat 2020 Jun;59(Suppl 1):73-80

1Clinical Department of Nuclear Medicine and Radiation Protection, Zagreb University Hospital Centre, Zagreb, Croatia; 2Clinical Department of Oncology, Zagreb University Hospital Centre, Zagreb, Croatia; 3The University of Zagreb School of Medicine, Zagreb, Croatia; 4The University of Zagreb School of Dental Medicine, Zagreb, Croatia.

Although most patients with thyroid cancer have a favorable clinical course, some patients develop a more aggressive type of cancer and exhibit more rapid disease progression with worse prognosis. Those patients usually exhibit mutations of proteins such as tyrosine kinase enzymes that play a significant role in regulation of tumor proliferation and spreading. Development of targeted therapies is based on the inhibition of mutated kinases which are involved in the MAPK signaling pathway. Read More

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eVIP2: Expression-based variant impact phenotyping to predict the function of gene variants.

PLoS Comput Biol 2021 Jul 2;17(7):e1009132. Epub 2021 Jul 2.

Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America.

While advancements in genome sequencing have identified millions of somatic mutations in cancer, their functional impact is poorly understood. We previously developed the expression-based variant impact phenotyping (eVIP) method to use gene expression data to characterize the function of gene variants. The eVIP method uses a decision tree-based algorithm to predict the functional impact of somatic variants by comparing gene expression signatures induced by introduction of wild-type (WT) versus mutant cDNAs in cell lines. Read More

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Regulatory Network Analysis of Mutated Genes Based on Multi-Omics Data Reveals the Exclusive Features in Tumor Immune Microenvironment Between Left-Sided and Right-Sided Colon Cancer.

Front Oncol 2021 15;11:685515. Epub 2021 Jun 15.

The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.

Left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have distinct characteristics in tumor immune microenvironment (TIME). Although existing studies have shown a strong association between gene mutations and TIME, whether the regulatory mechanisms between gene mutations and TIME are different between RCC and LCC is still unclear. In this study, we showed the fractions of CD8+ T cells were higher while those of regulatory T cells were lower in RCC. Read More

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A kinome-centered CRISPR-Cas9 screen identifies activated BRAF to modulate enzalutamide resistance with potential therapeutic implications in BRAF-mutated prostate cancer.

Sci Rep 2021 Jul 1;11(1):13683. Epub 2021 Jul 1.

Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Resistance to drugs targeting the androgen receptor (AR) signaling axis remains an important challenge in the treatment of prostate cancer patients. Activation of alternative growth pathways is one mechanism used by cancer cells to proliferate despite treatment, conferring drug resistance. Through a kinome-centered CRISPR-Cas9 screen in CWR-R1 prostate cancer cells, we identified activated BRAF signaling as a determinant for enzalutamide resistance. Read More

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Leptomeningeal Metastases from Solid Tumors: Recent Advances in Diagnosis and Molecular Approaches.

Cancers (Basel) 2021 Jun 9;13(12). Epub 2021 Jun 9.

Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy.

Leptomeningeal metastases (LM) from solid tumors represent an unmet need of increasing importance due to an early use of MRI for diagnosis and improvement of outcome of some molecular subgroups following targeted agents and immunotherapy. In this review, we first discussed factors limiting the efficacy of targeted agents in LM, such as the molecular divergence between primary tumors and CNS lesions and CNS barriers at the level of the normal brain, brain tumors and CSF. Further, we reviewed pathogenesis and experimental models and modalities, such as MRI (with RANO and ESO/ESMO criteria), CSF cytology and liquid biopsy, to improve diagnosis and monitoring following therapy. Read More

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Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma.

Cancers (Basel) 2021 Jun 18;13(12). Epub 2021 Jun 18.

Departement de Dermatologie, University of Montpellier, 34000 Montpellier, France.

Purpose: Melanoma's incidence is increasing, and elderly people could be significantly impacted since the majority occurs in people over 65 years of age. Combined BRAF and MEK targeted therapies (TT) are current standard regimen for BRAF mutated metastatic melanoma (MM). Except for subgroups of pivotal trials, little data are available for TT in this population. Read More

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NGS-Based Analysis of Atypical Deep Penetrating Nevi.

Cancers (Basel) 2021 Jun 19;13(12). Epub 2021 Jun 19.

Section of Pathological Anatomy, Department of Health Sciences, University of Florence, 50121 Firenze, Italy.

Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a diverse metastatic potential. We describe herein a cohort of 21 atypical DPNs analyzed by next-generation sequencing using the Ion AmpliSeq™ Comprehensive Cancer Panel. Read More

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Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma.

Int J Mol Sci 2021 Jun 23;22(13). Epub 2021 Jun 23.

Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Marymoncka 99/103, 01-813 Warsaw, Poland.

Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. Read More

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Comparison of Resistance Spectra after First and Second Line Osimertinib Treatment Detected by Liquid Biopsy.

Cancers (Basel) 2021 Jun 8;13(12). Epub 2021 Jun 8.

Institut für Hämatopathologie Hamburg, Fangdieckstraße 75A, 22547 Hamburg, Germany.

Since 2009, several first, second, and third generation tyrosine kinase inhibitors (TKI) have been approved for targeted treatment of mutated metastatic non-small lung cancer (NSCLC). A vast majority of patients is improving quickly on treatment; however, resistance is inevitable and typically occurs after one year for TKI of the first and second generation. Osimertinib, a third generation TKI, has recently been approved for first line treatment in the palliative setting and is expected to become approved for the adjuvant setting as well. Read More

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Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib.

Int J Mol Sci 2021 Jun 8;22(12). Epub 2021 Jun 8.

Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, 51000 Rijeka, Croatia.

BRAFV600E mutations are found in approximately 10% of colorectal cancer patients and are associated with worse prognosis and poor outcomes with systemic therapies. The aim of this study was to identify novel druggable features of BRAFV600E-mutated colon cancer (CC) cells associated with the response and resistance to BRAFV600E inhibitor vemurafenib. Towards this aim, we carried out global proteomic profiling of BRAFV600E mutant vs. Read More

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Genetic and phenotypic characteristics of Russian patients with BRAF-mutated colorectal cancer.

Neoplasma 2021 Jun 29. Epub 2021 Jun 29.

Ryzhykh National Medical Research Center of Coloproctology, Moscow, Russia.

Colorectal cancer (CRC) is one of the most common malignancies in the world. It's estimated about 1,8 M new CRC cases worldwide per year. A somatic mutation in the BRAF gene in the tumor is a negative prognostic factor. Read More

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Successful encorafenib desensitization in a patient with recurrent metastatic melanoma.

Melanoma Res 2021 08;31(4):402-404

Division of Allergic Diseases, Mayo Clinic, Rochester, Minnesota, USA.

Type I hypersensitivity reactions (HSR) to dabrafenib are rare but have been previously described. We present a case where a 72-year-old woman with recurrent, metastatic BRAF-mutated melanoma developed a type I HSR to dabrafenib. We, therefore, developed a desensitization protocol with encorafenib, a similar class agent, to allow the patient to continue with treatment. Read More

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Content of circulating tumor DNA depends on the tumor type and the dynamics of tumor size, but is not influenced significantly by physical exercise, time of the day or recent meal.

Cancer Genet 2021 Aug 28;256-257:165-178. Epub 2021 May 28.

N.N. Petrov Institute of Oncology, St. Petersburg 197758, Russia; St. Petersburg Pediatric Medical University, St. Petersburg 194100, Russia; I.I. Mechnikov North-Western Medical University, St. Petersburg 191015, Russia; St. Petersburg State University, St. Petersburg 199034, Russia. Electronic address:

Purpose: This study aimed to investigate factors, which influence the content of circulating tumor DNA (ctDNA).

Methods: 398 serial plasma samples were collected within 1-7 consecutive days from patients with EGFR-mutated lung cancer (n = 13), RAS/RAF-mutated colorectal cancer (n = 54) and BRAF-mutated melanoma (n = 17), who presented with measurable tumor disease. The amount of ctDNA was determined by ddPCR. Read More

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First line treatment of BRAF mutated advanced melanoma: Does one size fit all?

Cancer Treat Rev 2021 Jun 18;99:102253. Epub 2021 Jun 18.

Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy.

In the last decade, immunotherapy and target therapy have revolutionized the prognosis of patients with BRAF-V600 mutation-positive metastatic melanoma. To date, three different combinations of BRAF/MEK inhibitors have been approved for this population, showing comparable efficacy and unique toxicity profiles. Several immune-checkpoint inhibitors, including pembrolizumab, nivolumab and the combination of nivolumab plus ipilimumab, are also available options for untreated metastatic melanoma patients. Read More

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