Melanoma BRAF Inhibitors Review
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Melanoma BRAF Inhibitors Review
Zelboraf (vemurafenib, Roche) and Tafinlar (dabrafenib, GSK) get FDA and EMA approval for advanced metastatic melanoma. Several follow up BRAF inhibitors are in clinical development by rival pharma companies (Novartis, BMS, J&J, Teva) to get a share of expanding melanoma market and improve complete response rates and overcome resistance. Nexavar (sorafenib, Bayer) for for liver (HCC) and renal (RCC) cancer was the first approved and marketed BRAF inhibitor.
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Vemurafenib (PLX 4032, Roche) Melanoma: FDA Review & Approval - un knol de Krishan Maggon

Vemurafenib (PLX 4032, Roche) Melanoma: FDA Review & Approval - un knol de Krishan Maggon | Melanoma BRAF Inhibitors Review | Scoop.it
Only a single new investigation drug has produced a 81% response rate and extended overall survival by 7 months (range 2-18...
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Updated KEYTRUDA® (pembrolizumab) Data in Small Cell Lung Cancer and Mesothelioma Presented at 17th World Conference on Lung Cancer

Updated KEYTRUDA® (pembrolizumab) Data in Small Cell Lung Cancer and Mesothelioma Presented at 17th World Conference on Lung Cancer | Melanoma BRAF Inhibitors Review | Scoop.it
Updated KEYTRUDA® (pembrolizumab) Data in Small Cell Lung Cancer and Mesothelioma Presented at 17th World Conference on Lung Cancer
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Challenges in melanoma clinical research - Melanoma Institute Australia

Challenges in melanoma clinical research - Melanoma Institute Australia | Melanoma BRAF Inhibitors Review | Scoop.it
Despite the recent surge in therapy available for advanced melanoma, not all patients respond and researchers want to find out why.
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Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation

Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation | Melanoma BRAF Inhibitors Review | Scoop.it
In vitro , EGFR inhibition, combined with the BRAF inhibitor vemurafenib, causes synergistic cytotoxicity for BRAF V600E metastatic colorectal cancer, further augmented by irinotecan.
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Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma

Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma | Melanoma BRAF Inhibitors Review | Scoop.it
Abstract Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb). The combination of antigen-specific aAPC-based activation and anti-PD-1 mAb checkpoint blockade induced the greatest IFN-γ secretion by CD8+ T cells in vitro. Combination treatment also acted synergistically in an in vivo murine melanoma model to result in delayed tumor growth and extended survival, while either treatment alone had no effect. This was shown mechanistically to be due to decreased PD-1 expression and increased antigen-specific proliferation of CD8+ T cells within the tumor microenvironment and spleen. Thus, biomaterial-based therapy can synergize with other immunotherapies and motivates the translation of biomimetic combinatorial treatments. 

 Keywords Artificial antigen presenting cell; Immunotherapy; CD8+ T-cell; PD-1; Combination therapy
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Biomaterials Available online 2 December 2016 In Press, Accepted Manuscript
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Treatment of Metastatic Melanoma: A New World Opens - SkinCancer.org

Treatment of Metastatic Melanoma: A New World Opens - SkinCancer.org | Melanoma BRAF Inhibitors Review | Scoop.it
Melanoma is the deadliest form of skin cancer. When discovered early, it can usually be cured with surgery alone, but once it spreads (metastasizes) throughout the body, treatment options are limited.1 After decades of frustration for researchers, however, promising new therapies are providing hope, extending life by a year or two for many patients and in some cases virtually curing them.
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Combine and Conquer: Double CTLA-4 and PD-1 Blockade Combined with Whole Tumor Antigen Vaccine Cooperate to Eradicate Tumors

Combine and Conquer: Double CTLA-4 and PD-1 Blockade Combined with Whole Tumor Antigen Vaccine Cooperate to Eradicate Tumors | Melanoma BRAF Inhibitors Review | Scoop.it
Visit the Cancer Research 75th Anniversary [timeline][1].

See related article by Duraiswamy et al., [Cancer Res 2013;73:3591–603][2] .

Cancers hijack the normal regulatory pathways of normal inflammatory reactions.
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Tumor-specific delivery of biologics by a novel T-cell line HOZOT

Tumor-specific delivery of biologics by a novel T-cell line HOZOT | Melanoma BRAF Inhibitors Review | Scoop.it
“Cell-in-cell” denotes an invasive phenotype in which one cell actively internalizes in another.
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Researchers uncover a survival mechanism in cancer cells. ecancer - News

Researchers uncover a survival mechanism in cancer cells. ecancer - News | Melanoma BRAF Inhibitors Review | Scoop.it
Researchers uncover a survival mechanism in cancer cells. ecancer - News https://t.co/MuouZcFshY
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Targeting Immunosuppressive Cells May Boost Checkpoint Inhibitors

Targeting Immunosuppressive Cells May Boost Checkpoint Inhibitors | Melanoma BRAF Inhibitors Review | Scoop.it
Read how targeting immunosuppressive myeloid cells in tumors, using IPI-549, may be a way to stop cancers from evading immune system's cytotoxic T-cells.
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What is the future of melanoma immunotherapy

What is the future of melanoma immunotherapy | Melanoma BRAF Inhibitors Review | Scoop.it
Brigitte Dréno, MD, PhD from the University Hospital of Nantes, Nantes, France discusses vaccination and T-cell adoptive therapies for the treatment of melanoma at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the...
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CTLA-4 Limits Anti-CD20–Mediated Tumor Regression

CTLA-4 Limits Anti-CD20–Mediated Tumor Regression | Melanoma BRAF Inhibitors Review | Scoop.it
Purpose: The inhibition of tumor growth by anti-CD20 antibody (Ab) treatment is mediated by Ab- and complement-dependent cytotoxicity in xenograft tumor models.
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New Topical Immunotherapy Effective Against Early Skin Cancer

New Topical Immunotherapy Effective Against Early Skin Cancer | Melanoma BRAF Inhibitors Review | Scoop.it
A combination of two topical drugs that have been in use for years triggers a robust immune response against precancerous skin lesions, according to a new study. The research, from Washington University School of Medicine in St.
Krishan Maggon 's insight:
Cunningham TJ, Tabacchi M, Eliane JP, Tuchayi SM, Manivasagam S, Mirzaalian H, Turkoz A, Kopan R, Schaffer A, Saavedre AP, Wallendorf M, Cornelius LA, Demehri S. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. The Journal of Clinical Investigation. Nov. 21, 2016.
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Merck Laugh Its Way To The Bank With Breakthrough Drug Keytruda

Merck Laugh Its Way To The Bank With Breakthrough Drug Keytruda | Melanoma BRAF Inhibitors Review | Scoop.it
Cancer is the leading cause of death and it is a $147 billion market in 2018. Keytruda is a significant breakthrough for cancer treatment and it had netted sale
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Monoclonal Antibody Pembrolizumab bound by PD-1 by caseysteffen on Shapeways

Monoclonal Antibody Pembrolizumab bound by PD-1 by caseysteffen on Shapeways | Melanoma BRAF Inhibitors Review | Scoop.it
Monoclonal Antibody Pembrolizumab bound by PD-1 (YJ3JWGGA8) by caseysteffen on Shapeways. Learn more before you buy, or discover other cool products in Mathematical Art.
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Novel therapy starves the engine driving cancer cell growth | ERC: European Research Council

Novel therapy starves the engine driving cancer cell growth | ERC: European Research Council | Melanoma BRAF Inhibitors Review | Scoop.it
The main goal of the European Research Council (ERC) is to encourage high quality research in Europe through competitive funding
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Beating Cancer at Its Own Game | DiscoverMagazine.com

Beating Cancer at Its Own Game | DiscoverMagazine.com | Melanoma BRAF Inhibitors Review | Scoop.it
How an iconoclastic cancer researcher gamed the immune system and unleashed a potent new weapon against the disease.
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Treatment of melanoma skin cancer, by stage

Treatment of melanoma skin cancer, by stage | Melanoma BRAF Inhibitors Review | Scoop.it
American Cancer Society: The type of treatment(s) your doctor recommends will depend on the stage and location of the melanoma and on your overall health. Learn more here.
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Clinical Significance of Circulating CD33+CD11b+HLA-DR− Myeloid Cells in Patients with Stage IV Melanoma Treated with Ipilimumab

Clinical Significance of Circulating CD33+CD11b+HLA-DR− Myeloid Cells in Patients with Stage IV Melanoma Treated with Ipilimumab | Melanoma BRAF Inhibitors Review | Scoop.it
Purpose: High levels of circulating myeloid-derived suppressor cells (MDSCs) in various cancer types, including melanoma, were shown to correlate with poor survival.
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New strategy may drop cancer’s guard

New strategy may drop cancer’s guard | Melanoma BRAF Inhibitors Review | Scoop.it
A drug used now to treat Type 2 diabetes may someday beat breast and ovarian cancers, but not until researchers decode the complex interactions that in some cases help promote tumors.
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Rare, But Fatal, Case of Cardiac Toxicity on Yervoy/Opdivo Combo Reported

Rare, But Fatal, Case of Cardiac Toxicity on Yervoy/Opdivo Combo Reported | Melanoma BRAF Inhibitors Review | Scoop.it
Here, a study details a rare case of two people who died of cardiac inflammation after receiving Yervoy plus Opdivo combination therapy for melanoma.
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Fighting melanoma?

Fighting melanoma? | Melanoma BRAF Inhibitors Review | Scoop.it
Learn about a treatment option that works with your body's immune system to help fight advanced melanoma.
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The importance of biomarkers to optimize treatment with immunotherapy for melanoma

The importance of biomarkers to optimize treatment with immunotherapy for melanoma | Melanoma BRAF Inhibitors Review | Scoop.it
Paolo Ascierto, MD of the National Tumor Institute Fondazione G.
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Rapid and continued T cell differentiation into long-term effector and memory stem cells in vaccinated melanoma patients. - PubMed - NCBI

Rapid and continued T cell differentiation into long-term effector and memory stem cells in vaccinated melanoma patients. - PubMed - NCBI | Melanoma BRAF Inhibitors Review | Scoop.it
Clin Cancer Res. 2016 Nov 21. pii: clincanres.1708.2016. [Epub ahead of print]
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BRAF inhibitor: targeted therapy in hairy cell leukemia

BRAF inhibitor: targeted therapy in hairy cell leukemia | Melanoma BRAF Inhibitors Review | Scoop.it
In this issue of Blood , [Dietrich et al][1] report that the low-dose BRAF inhibitor, vemurafenib, is highly effective in refractory hairy cell leukemia.[1][2]

![Figure][3]

The activated BRAF pathway provides oncogenic signaling to the leukemic hairy cell through the MEK-ERK cascade.
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Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design

Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design | Melanoma BRAF Inhibitors Review | Scoop.it
Abstract KRAS is the most frequently mutated oncogene in human cancer. In addition to holding this distinction, unsuccessful attempts to target this protein have led to the characterization of RAS as 'undruggable'. However, recent advances in technology and novel approaches to drug discovery have renewed hope that a direct KRAS inhibitor may be on the horizon. In this Review, we provide an in-depth analysis of the structure, dynamics, mutational activation and inactivation, and signalling mechanisms of RAS. From this perspective, we then consider potential mechanisms of action for effective RAS inhibitors. Finally, we examine each of the many recent reports of direct RAS inhibitors and discuss promising avenues for further development.
Krishan Maggon 's insight:
Nat Rev Drug Discov. 2016 Nov;15(11):771-785. doi: 10.1038/nrd.2016.139. Epub 2016 Jul 29. 

Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design. 

Ostrem JM, Shokat KM.
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