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Vemurafenib

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https://www.readbyqxmd.com/read/28224120/oncolytic-virotherapy-including-rigvir-and-standard-therapies-in-malignant-melanoma
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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)...
February 6, 2017: Oncologist
https://www.readbyqxmd.com/read/28153858/drug-combo-beats-vemurafenib-for-colorectal-cancer
#8
(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
https://www.readbyqxmd.com/read/28151482/critical-role-of-reactive-oxygen-species-ros-for-synergistic-enhancement-of-apoptosis-by-vemurafenib-and-the-potassium-channel-inhibitor-tram-34-in-melanoma-cells
#9
Daniel Bauer, Felix Werth, Ha An Nguyen, Felix Kiecker, Jürgen Eberle
Inhibition of MAP kinase pathways by selective BRAF inhibitors, such as vemurafenib and dabrafenib, have evolved as key therapies of BRAF-mutated melanoma. However, tumor relapse and therapy resistance have remained as major problems, which may be addressed by combination with other pathway inhibitors. Here we identified the potassium channel inhibitor TRAM-34 as highly effective in combination with vemurafenib. Thus apoptosis was significantly enhanced and cell viability was decreased. The combination vemurafenib/TRAM-34 was also effective in vemurafenib-resistant cells, suggesting that acquired resistance may be overcome...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28150343/vemurafenib-induced-toxic-epidermal-necrolysis-is-it-an-emerging-side-effect-of-the-drug
#10
S Kılıç, E Özkaya, C Baykal, S Vatansever
Vemurafenib, a selective inhibitor of the BRAF-kinase used in treatment of metastatic melanoma alone or in combinations,(1) is known to cause various adverse skin reactions such as maculopapular rash, photosensitivity and hyperkeratotic lesions, affecting more than 90% of patients.(1-2) Severe adverse reactions were observed in less than 1% of the patients in clinical trials.(3) However, the increasing number of reported cases of vemurafenib-induced toxic epidermal necrolysis (TEN), a life-threatening severe cutaneous adverse reaction, is striking...
February 1, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28129674/braf-inhibitor-associated-cutaneous-squamous-cell-carcinoma-new-mechanistic-insight-emerging-evidence-for-a-viral-involvement-and-perspectives-on-clinical-management
#11
REVIEW
J H Wu, D N Cohen, P L Rady, S K Tyring
Mutations in the BRAF proto-oncogene occur in the majority of cutaneous melanomas. The commonly detected valine (V) to glutamate (E) mutation (V600E) is known to drive melanomagenesis and has thus been the target of two highly selective chemotherapeutic agents: vemurafenib and dabrafenib. While BRAF inhibitor therapy has revolutionized the treatment of metastatic melanoma, unanticipated cutaneous toxicities including the development of cutaneous squamous cell carcinomas (cSCCs) are frequently reported and hinder therapeutic durability...
January 27, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28112278/cobimetinib-inhibiting-mek1-2-in-braf-v600-mutant-melanoma
#12
A Jimeno, J R Eagles
Historically, metastatic melanoma has had extremely poor survival outcomes. The outlook, however, is rapidly changing as new molecularly targeted therapies have vastly improved patient outcomes. One such therapy is the potent mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor cobimetinib. Recently, cobimetinib was approved for the treatment of metastatic or unresectable melanoma with serine/threonine-protein kinase B-raf (BRAF) V600E or V600K mutations when used in combination with the BRAF inhibitor vemurafenib...
November 2016: Drugs of Today
https://www.readbyqxmd.com/read/28107182/the-nitrobenzoxadiazole-derivative-mc3181-blocks-melanoma-invasion-and-metastasis
#13
Anastasia De Luca, Debora Carpanese, Maria Cristina Rapanotti, Tara Mayte Suarez Viguria, Maria Antonietta Forgione, Dante Rotili, Chiara Fulci, Egidio Iorio, Luigi Quintieri, Sergio Chimenti, Luca Bianchi, Antonio Rosato, Anna Maria Caccuri
The novel nitrobenzoxadiazole (NBD) derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Here, we report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. The strong antimetastatic activity of MC3181 was observed in both 2D monolayer cultures and 3D multicellular tumor spheroids, and confirmed in vivo by the significant decrease in the number of B16-F10 melanoma lung metastases in drug-treated mice...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106277/tumor-targeting-salmonella-typhimurium-a1-r-sensitizes-melanoma-with-a-braf-v600e-mutation-to-vemurafenib-in-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#14
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Ming Zhao, Yong Zhang, Bartosz Chmielowski, Tasuku Kiyuna, Scott D Nelson, Tara A Russell, Sarah M Dry, Yunfeng Li, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
Previously, a BRAF-V600E-mutant melanoma obtained from the right chest wall of a patient was grown orthotopically in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. Tumor sizes were measured with calipers twice a week. On day 14 from initiation of treatment, trametinib (TRA), an MEK inhibitor, caused tumor regression. In contrast, another MEK inhibitor, cobimetinib (COB) could slow but not arrest growth or cause regression of the melanoma. First-line therapy temozolomide (TEM) could slow but not arrest tumor growth or cause regression...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28100090/patterns-of-use-of-systemic-therapies-among-patients-with-metastatic-melanoma-a-retrospective-claims-database-analysis-in-the-united-states
#15
Qiufei Ma, Yaozhu Juliette Chen, Dionne M Hines, Julie Munakata, Nicolas Batty, Beth Louise Barber, Zhongyun Zhao
OBJECTIVES: This retrospective analysis of the IMS PharMetrics Plus claims database aimed to describe the current real-world treatment patterns for metastatic melanoma in the USA. METHODS: Included patients (aged ≥18 years) had ≥1 prescription for ipilimumab, vemurafenib, temozolomide or dacarbazine between 1 January 2011 and 31 August 2013; diagnosis of melanoma and metastasis before first use (index date); no index drug use prior to the index date; continuous health plan enrollment for ≥6 months before and ≥3 months after index date...
January 19, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28099231/vemurafenib-braf-inhibitor-therapy-for-orbital-erdheim-chester-disease
#16
Adit Gupta, Amir Yeganeh, Daniel Rootman, Robert Goldberg
Erdheim-Chester disease is a rare xanthogranulomatous systemic disease, which involves the orbit in some cases. Through this case report, the authors review the treatment modalities used in orbital Erdheim-Chester disease and explore a newer modality of treatment. Cases of orbital Erdheim-Chester disease were identified in the literature utilizing a PubMed search and all the treatment modalities were reviewed. The response to treatment of orbital Erdheim-Chester disease has been poor with the various medical and surgical treatment modalities used in the past...
January 17, 2017: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28094001/autophagy-inhibition-overcomes-multiple-mechanisms-of-resistance-to-braf-inhibition-in-brain-tumors
#17
Jean M Mulcahy Levy, Shadi Zahedi, Andrea M Griesinger, Andrew Morin, Kurtis D Davies, Dara L Aisner, B K Kleinschmidt-DeMasters, Brent E Fitzwalter, Megan L Goodall, Jacqueline Thorburn, Vladimir Amani, Andrew M Donson, Diane K Birks, David M Mirsky, Todd C Hankinson, Michael H Handler, Adam L Green, Rajeev Vibhakar, Nicholas K Foreman, Andrew Thorburn
Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor resistance mechanisms in brain tumors. BRAF(V600E)mutations occur in many pediatric brain tumors. We previously reported that these tumors are autophagy-dependent and a patient was successfully treated with the autophagy inhibitor chloroquine after failure of the BRAF(V600E) inhibitor vemurafenib, suggesting autophagy inhibition overcame the kinase inhibitor resistance...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28093487/a-pilot-trial-of-the-combination-of-vemurafenib-with-adoptive-cell-therapy-in-patients-with-metastatic-melanoma
#18
Drew C Deniger, Mei Li M Kwong, Anna Pasetto, Mark E Dudley, John R Wunderlich, Michelle M Langhan, Chyi-Chia Richard Lee, Steven A Rosenberg
PURPOSE: This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF(V600) mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. EXPERIMENTAL DESIGN: A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#19
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28072717/clinics-prognosis-and-new-therapeutic-options-in-patients-with-mucosal-melanoma-a-retrospective-analysis-of-75-patients
#20
Tim Schaefer, Imke Satzger, Ralf Gutzmer
Mucosal melanomas represent a rare entity with different risk factors and molecular features compared to cutaneous melanomas. They arise most commonly from mucosal surfaces in the head/neck region, the female genital tract (FGT) and the anorectal region. The aim of this study was to evaluate clinics, prognosis, and treatment options of patients with mucosal melanoma, in particular with regard to different primary sites.We retrospectively analyzed 75 patients with mucosal melanomas diagnosed in the years 1993 to 2015 in our department...
January 2017: Medicine (Baltimore)
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