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Vemurafenib

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https://www.readbyqxmd.com/read/28345133/second-primary-melanoma-on-a-patient-undergoing-vemurafenib-therapy-a-case-report
#1
Giuliana Onnis, Giuseppe Palmieri, Maria Antonietta Montesu, Rosanna Satta
BACKGROUND: Several side effects have been reported during treatment with vemurafenib, including multiple benign lesions and, less frequently, atypical melanocytic proliferations and second primary melanomas. METHODS: A 46-year-old man undergoing vemurafenib therapy for metastatic malignant melanoma was clinically and dermoscopically monitored using total-body mapping. RESULTS: During BRAF inhibitor (BRAFi) treatment, the patient developed atypical melanocytic lesions and particularly secondary primary melanoma...
March 26, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28303522/nanotechnology-for-the-treatment-of-melanoma-skin-cancer
#2
REVIEW
Lucas B Naves, Chetna Dhand, Jayarama Reddy Venugopal, Lakshminarayanan Rajamani, Seeram Ramakrishna, Luis Almeida
Melanoma is the most aggressive type of skin cancer and has very high rates of mortality. An early stage melanoma can be surgically removed, with a survival rate of 99%. This literature review intends to elucidate the possibilities to treat melanoma skin cancer using hybrid nanofibers developed by advanced electrospinning process. In this review we have shown that the enhanced permeability and retention is the basis for using nanotechnology, aiming topical drug delivery. The importance of the detection of skin cancer in the early stages is directly related to non-metastatic effects and survival rates of melanoma cells...
March 16, 2017: Progress in biomaterials
https://www.readbyqxmd.com/read/28297625/genomics-of-hairy-cell-leukemia
#3
Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28295542/unexpected-recalcitrant-course-of-drug-induced-erythema-multiforme-like-eruption-and-interstitial-pneumonia-sequentially-occurring-after-nivolumab-therapy
#4
Hisashi Nomura, Hayato Takahashi, Satsuki Suzuki, Yuichi Kurihara, Shotaro Chubachi, Ichiro Kawada, Hiroyuki Yasuda, Tomoko Betsuyaku, Masayuki Amagai, Takeru Funakoshi
Vemurafenib improves survival of melanoma patients. However, cutaneous side-effects commonly occur in them. Nivolumab and ipilimumab are monoclonal antibodies against programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4, both of which regulate excessive T-cell activation. Although these agents induce antitumor immunity against melanoma, the modified immune condition may result in an unexpected adverse reaction which has not been observed previously. Herein, we report a case who manifested severe erythema multiforme-like eruption with mucosal involvement associated with vemurafenib following nivolumab...
March 11, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28293855/growth-hormone-receptor-knockdown-sensitizes-human-melanoma-cells-to-chemotherapy-by-attenuating-expression-of-abc-drug-efflux-pumps
#5
Reetobrata Basu, Nicholas Baumgaertel, Shiyong Wu, John J Kopchick
Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action...
March 14, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28268124/-usefulness-of-nuclear-medicine-in-erdheim-chester-disease-a-lille-experience
#6
A Adens, P Landy, L Terriou, C Baillet, A Beron, M Lambert, D Launay, D Huglo
INTRODUCTION: Erdheim-Chester disease is a rare form of non-langerhans histiocytosis and its etiology is still not well established. The aims of the study were to assess the value of the bone scintigraphy and the (18)F-FDG PET/CT for the diagnostic and for the latter in the therapeutic evaluation. METHODS: We retrospectively reviewed 49 patients suspected of Erdheim-Chester disease between 2004 and 2016. Bone scintigraphy was compared with histopathology and PET-CT to conventional morphological examinations and bone scintigraphy...
March 3, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28263969/activated-mek-cooperates-with-cdkn2a-and-pten-loss-to-promote-the-development-and-maintenance-of-melanoma
#7
H Yang, D A Kircher, K H Kim, A H Grossmann, M W VanBrocklin, S L Holmen, J P Robinson
The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical outcome for melanoma patients with BRAF(V600E) mutations. Although the initial response to these inhibitors can be dramatic, sometimes causing complete tumor regression, the majority of melanomas eventually become resistant. Mitogen-activated protein kinase kinase (MEK) mutations are found in primary melanomas and frequently reported in BRAF melanomas that develop resistance to targeted therapy; however, melanoma is a molecularly heterogeneous cancer, and which mutations are drivers and which are passengers remains to be determined...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28262109/adult-xanthogranulomatous-disease-of-the-orbit-clinical-presentations-evaluation-and-management
#8
J M Ortiz Salvador, D Subiabre Ferrer, A Pérez Ferriols
Adult xanthogranulomatous disease of the orbit refers to a heterogeneous group of clinical syndromes with differing degrees of systemic involvement and distinct prognoses. The different syndromes all present clinically with progressively enlarging, yellowish lesions of the orbit. Histologically, the lesions are characterized by an inflammatory infiltrate of foam cells and Touton-type multinucleated giant cells. The xanthomatized histiocytes are CD68(+), S100(-), and CD1a(-). There are 4 clinical forms of xanthogranulomatous disease of the orbit: adult xanthogranulomatous disease of the orbit, adult onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease...
March 2, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/28255850/clinical-pharmacokinetics-of-vemurafenib
#9
REVIEW
Weijiang Zhang, Dominik Heinzmann, Joseph F Grippo
Vemurafenib is an orally administered small-molecule inhibitor of the oncogenic BRAF kinase that is indicated for the treatment of patients with unresectable or metastatic melanoma harbouring BRAF (V600) mutations. Vemurafenib is absorbed rapidly after a single oral dose of 960 mg, reaching maximum drug concentration approximately 4 h after administration. Extensive accumulation occurs after multiple dosing at 960 mg twice daily. Steady state is achieved after approximately 15-21 days and exposure at steady state is relatively constant...
March 2, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28255242/braf-v600-mutations-in-solid-tumors-other-than-metastatic-melanoma-and-papillary-thyroid-cancer-or-multiple-myeloma-a-screening-study
#10
Allen L Cohn, Bann-Mo Day, Sarang Abhyankar, Edward McKenna, Todd Riehl, Igor Puzanov
BACKGROUND: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer) or multiple myeloma harboring activating BRAF(V600) mutations for enrollment in a vemurafenib clinical study. METHODS: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAF(V600) mutations by bidirectional direct Sanger sequencing...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28252478/response-of-braf-inhibitor-associated-squamous-cell-lung-carcinoma-to-drug-withdrawal
#11
Jonathan T Blackmon, Ratika Dhawan, Nina L Terry, Robert M Conry
Vemurafenib and dabrafenib, two Food and Drug Administration-approved selective BRAF kinase inhibitors (BRAFi), have revolutionized the targeted therapy of cutaneous melanoma. Off-target effects of these drugs paradoxically activate the MAP kinase pathway in BRAF wild-type cells, leading to secondary malignancies. Although cutaneous squamous cell carcinomas are by far the most frequent, emergence of potentially life-threatening secondary tumors from other sites following prolonged therapy is a growing concern...
April 2017: Melanoma Research
https://www.readbyqxmd.com/read/28249088/braf-v600e-mutation-in-involuting-nevus-in-a-patient-treated-with-vemurafenib
#12
José Francisco Millán-Cayetano, Inés Fernández-Canedo, Nuria Blázquez-Sánchez, Rafael Fúnez-Liébana, Magdalena de Troya-Martín
No abstract text is available yet for this article.
March 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28224120/oncolytic-virotherapy-including-rigvir-and-standard-therapies-in-malignant-melanoma
#13
REVIEW
Hani M Babiker, Irbaz Bin Riaz, Muhammad Husnain, Mitesh J Borad
The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28222655/a-cytologic-diagnosis-of-braf-v600e-erdheim-chester-disease-on-pericardial-fluid
#14
P Chasseur, M Kyriakopoulou, B Vokaer, I Beukinga, R Casado Arroyo, E Cogan, B Couturier
We report the case of a 74-year-old woman admitted to the emergency unit for resting dyspnea. Clinical presentation, cardiac MRI and echocardiography were consistent with cardiac tamponade requiring emergency pericardiocentesis. Cytologic examination of the pericardial fluid revealed the presence of CD68(pos) CD1a(neg) S100(neg) foamy histiocytes (Fig. 1). Additional investigations complied with the diagnosis of Erdheim-Chester histiocytosis. Treatment with αIFN was initiated but the patient developed severe neutropenia that contraindicated further administration...
February 22, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28211633/painful-nipple-hyperkeratosis-secondary-to-vemurafenib
#15
Emily S Carr, Shannon C Brown, Katherine H Fiala
Vemurafenib is a selected BRAF kinase inhibitor approved for treating metastatic or unresectable melanoma, which has numerous cutaneous side effects unfortunately, including three previously reported cases of asymptomatic areola and/or nipple hyperkeratosis. We present the first case of painful bilateral nipple hyperkeratosis secondary to vemurafenib in an 84-year-old woman. She was successfully treated with tretinoin 0.05% cream that allowed her to comfortably continue treatment. With increased awareness of this condition, we found a second case of asymptomatic nipple hyperkeratosis secondary to vemurafenib in our clinic...
February 17, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28188228/time-resolved-phosphoproteome-analysis-of-paradoxical-raf-activation-reveals-novel-targets-of-erk
#16
Peter Kubiniok, Hugo Lavoie, Marc Therrien, Pierre Thibault
Small molecules targeting aberrant RAF activity, like Vemurafenib (PLX4032), are highly effective against cancers harboring the V600E BRAF mutation, and are now approved for clinical use against metastatic melanoma. However, in tissues showing elevated RAS activity and in RAS-mutant tumors, these inhibitors stimulate RAF dimerization, resulting in inhibitor resistance and downstream paradoxical ERK activation. To understand the global signaling response of cancer cells to RAF inhibitors, we profiled the temporal changes of the phosphoproteome of two colon cancer cell lines (Colo205 and HCT116) that respond differently to Vemurafenib...
February 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28182116/effective-braf-inhibitor-vemurafenib-therapy-in-a-2-year-old-patient-with-sequentially-diagnosed-langerhans-cell-histiocytosis-and-erdheim-chester-disease
#17
Zsófia Váradi, Rita Bánusz, Judit Csomor, Krisztián Kállay, Edit Varga, Gabriella Kertész, Monika Csóka
Erdheim-Chester disease (ECD) is a rare histiocytic disorder, characterized by the xanthomatous infiltration of tissues by CD68-positive and CD1a-/CD100-negative foamy histiocytes. In childhood, ECD is exceptionally rare, and only a dozen cases have been published so far. The cooccurence of Langerhans cell histiocytosis (LCH) and ECD is even rarer. Here, we report a 2-year-old boy, the youngest patient in the literature so far, who was diagnosed with concomitant BRAF mutation-positive LCH and ECD. In his case, conventional LCH treatment proved to be ineffective, but he is the youngest patient who was successfully treated with the BRAF inhibitor vemurafenib...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28173755/melanoma-genome-evolution-across-species
#18
Emily R Kansler, Akanksha Verma, Erin M Langdon, Theresa Simon-Vermot, Alexandra Yin, William Lee, Marc Attiyeh, Olivier Elemento, Richard M White
BACKGROUND: Cancer genomes evolve in both space and time, which contributes to the genetic heterogeneity that underlies tumor progression and drug resistance. In human melanoma, identifying mechanistically important events in tumor evolution is hampered due to the high background mutation rate from ultraviolet (UV) light. Cross-species oncogenomics is a powerful tool for identifying these core events, in which transgenically well-defined animal models of cancer are compared to human cancers to identify key conserved alterations...
February 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28167569/use-of-systemic-therapy-concurrent-with-cranial-radiotherapy-for-cerebral-metastases-of-solid-tumors
#19
Maikel Verduin, Jaap D Zindler, Hanneke M A Martinussen, Rob L H Jansen, Sander Croes, Lizza E L Hendriks, Danielle B P Eekers, Ann Hoeben
The incidence of brain metastases of solid tumors is increasing. Local treatment of brain metastases is generally straightforward: cranial radiotherapy (e.g., whole-brain radiotherapy or stereotactic radiosurgery) or resection when feasible. However, treatment becomes more complex when brain metastases occur while other metastases, outside of the central nervous system, are being controlled with systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies). It is known that some anticancer agents can increase the risk for neurotoxicity when used concurrently with radiotherapy...
February 2017: Oncologist
https://www.readbyqxmd.com/read/28153858/drug-combo-beats-vemurafenib-for-colorectal-cancer
#20
(no author information available yet)
Vemurafenib doesn't shrink BRAF-mutated colorectal tumors, but a regimen that also includes irinotecan and cetuximab improves vemurafenib's effectiveness, more than doubling progression-free survival in patients with metastatic tumors. The drug trio also increases disease-control rates.
February 2, 2017: Cancer Discovery
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