Braf Targets In Melanoma

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Braf Targets In Melanoma

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Author : Ryan J. Sullivan
language : en
Publisher: Springer
Release Date : 2014-11-24

Braf Targets In Melanoma written by Ryan J. Sullivan and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-11-24 with Medical categories.

​This volume contains a collection of writings from the leaders in the fields of Molecular Biology and Melanoma Research which will begin to tell the ever-expanding story of the most recent findings, discoveries, and potential of BRAF-directed targets in melanoma. Recent research has shown that BRAF inhibitors are effective for a short period of time, but there is little hope that this drugs as single agents will lead to durable benefit in a majority of patients. Among scientists and researchers who work in drug discovery, there is a lot of interest in the development of molecularly targeted cancer agents. Namely, the identification of a molecular target, the selection of molecules which effectively inhibit this target. What is starkly different about the development of this class of compounds, however, is that the mechanism of action of these agents are not as straightforward as was once previously assumed and the mechanisms of resistance that tumor cells employ to evade complete destruction are unlike any that have been described before. These discoveries in addition to utilization of modern molecular biology techniques have led to a series of hypotheses regarding which other types of molecules could be used in combination with BRAF-inhibitors in hopes of revolutionizing the potential of therapeutics in melanoma.

Braf Mutation As A Target For Treatment Of Melanoma

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Author : Andrea Aquilato
language : en
Publisher:
Release Date : 2012

Braf Mutation As A Target For Treatment Of Melanoma written by Andrea Aquilato and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.

Cutaneous Melanoma

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Author : Charles M. Balch
language : en
Publisher: Springer
Release Date : 2020-01-29

Cutaneous Melanoma written by Charles M. Balch and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-01-29 with Medical categories.

Written by the leading melanoma experts from the United States, Australia, and Europe, this new edition incorporates the clinical outcomes of more than 70,000 patients treated at major melanoma centers throughout the world and is the definitive and most authoritative textbook on melanoma used worldwide. Providing the most up-to-date and comprehensive information needed for the clinical management and scientific study of melanoma, Cutaneous Melanoma, 6th edition covers everything from precursors of melanoma to advanced stages of metastatic disease.

Melanoma

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Author : William H. Sharfman, MD
language : en
Publisher: Demos Medical Publishing
Release Date : 2012-12-17

Melanoma written by William H. Sharfman, MD and has been published by Demos Medical Publishing this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-17 with Medical categories.

This issue of Emerging Cancer Therapeutics provides a comprehensive review for practitioners on the current status of melanoma treatment. Due to recent drug approvals and increasing ability to offer combined agents, there are many more treatment options available to melanoma patients than even a few years ago. Especially significant are the recent FDA approval of the immunotherapeutic agent ipilimumab for metastatic melanoma, and new agents targeting the BRAF gene in malignant melanoma (these two developments cited among the top 5 most significant advances in oncology for 2011). There is also coverage of the most recent data pertaining to surgical management, staging and prevention, and melanoma in children. The authorship of the articles is outstanding and represents national and global authorities on the topics reviewed.

Melanoma

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Author : Guy Huynh Thien Duc
language : en
Publisher: BoD – Books on Demand
Release Date : 2013-01-30

Melanoma written by Guy Huynh Thien Duc and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-01-30 with Medical categories.

The Book "Melanoma - From Early Detection To Treatment" is aiming to present data and knowledge from most experienced experts in the field. The book covers main topics from the fundamental aspects to multiple approaches in the disease treatment as well as related features. It offers a global view concerning one of the most frequent types of cancer to which a substantial high proportion of people worldwide is confronted at some time point in life.

Human Skin Cancers

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Author : Miroslav Blumenberg
language : en
Publisher: BoD – Books on Demand
Release Date : 2018-05-02

Human Skin Cancers written by Miroslav Blumenberg and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-05-02 with Medical categories.

Human skin cancers, the most common type of tumors, represent a significant health burden. The deadliest is unquestionably melanoma. Half of melanomas have an activating mutation in the BRAF gene, prompting development of novel drugs, vemurafenib and dabrafenib, specifically targeting mutated BRAF. Trametinib and cobimetinib, which block MEK, a BRAF effector protein, have been used in combination with BRAF inhibitors. A promising new melanoma treatment is immunotherapy, approach that boosts patient's own immune system to attack cancer. Pembrolizumab and nivolumab inhibit PD-1, whereas Ipilimumab targets CTLA-4, another immunity check point, to boost the immune response. Here we focus on pathways, mechanisms, targets and treatments of human skin cancers, with particular emphasis on the new developments in the research on melanomas.

Identification Of Molecular Targets Of Oncogenic Nras And Braf Involved In Regulation Of Melanoma Cell Proliferation

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Author : Carlotta Petti
language : en
Publisher:
Release Date : 2007

Identification Of Molecular Targets Of Oncogenic Nras And Braf Involved In Regulation Of Melanoma Cell Proliferation written by Carlotta Petti and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with Melanoma categories.

Diagnostic And Prognostic Biomarkers And Therapeutic Targets In Melanoma

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Author : Michael J. Murphy
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-12-02

Diagnostic And Prognostic Biomarkers And Therapeutic Targets In Melanoma written by Michael J. Murphy and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-12-02 with Medical categories.

This book describes both the technologies used in the discovery of melanoma biomarkers and the clinical application of these biomarkers for diagnosis and staging of disease, determination of prognosis, treatment planning, monitoring of response to therapy, identification of novel therapeutic targets and drug development. A broad range of biomarkers (DNA/chromosomal, mRNA, microRNA, mitochondrial DNA, epigenetic and protein) is outlined. As therapies for melanoma become increasingly more target specific, the identification, validation and use of biomarkers will invariably play a greater role in the management of patients with this disease. Diagnostic and Prognostic Biomarkers and Therapeutic Targets in Melanoma is an essential resource for oncologists, dermatologists, dermatopathologists, general pathologists with an interest in melanoma, and melanoma researchers.

Genetics Of Melanoma

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Author : Carlos A. Torres-Cabala
language : en
Publisher: Springer
Release Date : 2016-05-11

Genetics Of Melanoma written by Carlos A. Torres-Cabala and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-05-11 with Medical categories.

This book discusses the molecular, biological, pathological, and clinical aspects of melanoma, with special emphasis in the new concepts of melanoma genetics. A multidisciplinary group of experts in Genetics, Dermatology, Pathology, and Melanoma Medical Oncology contribute state-of-the-art knowledge in melanoma research and clinical management, not only exposing the current status of knowledge of the topics but also providing their personal experiences and ideas about the future and potential practical application of the genetic aspects of melanoma. During the last few years we have witnessed an impressive amount of discoveries in the field of melanoma genetics which have changed our approach in understanding the pathogenesis and treatment of this lethal disease. Genetics of Melanoma is a practical approach to melanoma genetic mechanisms and their application in the diagnosis and treatment of this malignancy. It is an essential source of updated information and a powerful tool for clinicians, pathologists, and basic scientists who wish to understand, apply, and investigate the multiple new aspects of melanoma genetics.

Ctgf Is A Therapeutic Target For Metastatic Melanoma

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Author : Tiffany Roshea Williams
language : en
Publisher:
Release Date : 2015

Ctgf Is A Therapeutic Target For Metastatic Melanoma written by Tiffany Roshea Williams and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.

While only representing 4% of all skin cancers, melanoma accounts for over 70% of skin cancer deaths. Once metastasized, melanoma patient prognosis is poor with a median survival of 6 -15 months and a five-year survival rate of less than 5%. Clinically, low oxygen, or hypoxia, signaling has been associated with poor outcome in many solid tumors, including melanoma, and is a key factor regulating melanoma metastasis. Using microarray technology to identify mechanisms by which hypoxia promotes metastasis and potential therapeutic targets, we identified connective tissue growth factor (CTGF) as a gene differentially expressed in hypoxia (2% O2)-treated metastatic melanoma cells compared to normal oxygen conditions, or normoxia (21% O2). CTGF is a secreted, matricellular, and multimodular protein that interacts with many binding partners in the extracellular matrix (ECM) to modulate various cellular functions such as ECM production, cell adhesion, migration, proliferation, and survival. CTGF has been implicated in various pathological conditions and its involvement in the tumor progression of various human cancers has been demonstrated. Clinically, we observe that CTGF expression correlates with melanoma tumor progression. On this finding, we hypothesize that CTGF, as a modulator of multiple cellular functions, may represent a potential target for therapy for melanoma. Herein we identify CTGF as a hypoxia-inducible target gene through HIF-dependent mechanisms. Next, we elucidate the biological role and therapeutic potential of targeting CTGF in metastatic melanoma. In vitro, we observe that genetic inhibition of CTGF reduces the metastatic potential of metastatic melanoma cells by inhibiting migration, invasion, and anchorage-independent growth. In vivo, we use genetic or therapeutic inhibition (FG-3019, a human monoclonal antibody to CTGF, FibroGen) of CTGF in orthotopic melanoma mouse models and metastasis tail vein mouse models in order to determine the therapeutic potential of targeting CTGF. We observe that CTGF inhibition significantly reduces primary tumor growth and metastasis, suggesting that CTGF plays an important role in the aggressive phenotype of metastatic melanoma. To further explore the therapeutic potential of targeting CTGF in melanoma, we determine if CTGF can be targeted as a therapy in BRAF-inhibitor resistance melanoma. Several of the recent FDA-approved therapies for metastatic melanoma, including Vemurafenib (PLX4032), are small molecule inhibitors against the mutant form of BRAF, BRAFV600E, which is mutated in 50% of melanomas. Despite recent advances with these novel therapies, clinical benefit is short-lived, and many patients develop resistance within 5-7 months. Strikingly, we find that CTGF expression is significantly upregulated at the RNA and protein level in PLX4032-resistant cells compared to their PLX4032-sensitive matched cells. Functionally, inhibition of CTGF is sufficient to significantly decrease the enhanced metastatic behavior of the PLX-resistant cell lines. Importantly, in vivo, we observe that genetic inactivation of CTGF reduces the growth of PLX402-resistant melanoma primary tumors. In summary, this thesis has unveiled a novel therapy for metastatic melanoma. Our results are the first pre-clinical validation of CTGF as a therapeutic target for metastatic melanoma. This is also the first implication of CTGF as a target for therapy for patients who are unresponsive to BRAF inhibitor therapies. Our work is important because new melanoma therapies with long-term clinical benefits are needed. Future studies to elucidate the precise molecular mechanism through which CTGF promotes the aggressive phenotype of melanoma are currently ongoing. Additionally, the therapeutic efficacy of CTGF in combination with current melanoma therapeutics and in other genetic and drug resistant subtypes of melanoma is also being explored.