Download or read book Exploring Novel Strategies to Sensitize Melanoma to Immunotherapy and Targeted Therapies written by Fan Huang and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Melanoma is the deadliest form of skin cancer. Current treatments for patients with metastatic melanoma include checkpoint blockade immunotherapies and MAPK pathway-targeted therapies. However, innate and acquired resistance are common, presenting a major clinical challenge. Melanomas exhibit high intratumoral heterogeneity and cancer cell plasticity. The ability to switch between different cell states, a process known as phenotype switching, confers an advantage for melanoma cells to metastasize and acquire therapy resistance. Understanding the molecular and genetic determinants of melanoma plasticity is therefore critical for the development of improved and novel treatment regimens. In this thesis, I aimed to explore novel strategies to target melanoma plasticity and sensitize melanoma to therapy. We first investigated the role of the MNK1/2-eIF4E axis, an essential regulator of mRNA translation initiation, in melanoma phenotype switching and immune evasion. We demonstrated that blocking the MNK1/2-eIF4E axis inhibited melanoma switching from a proliferative to an invasive state and sensitized melanoma to anti-PD-1 immunotherapy. Phospho-eIF4E-deficient melanomas were characterized as expressing high levels of melanocytic antigens, producing less inflammatory cytokines, and being more infiltrated with CD8+ T cells. Mechanistically, we identified phospho-eIF4E-mediated translational control of NGFR, a critical effector of phenotype switching. In addition, genetic and pharmacological ablation of tumor cell-extrinsic phospho-eIF4E decreased PD-L1 expression on DCs and MDSCs, thus permitting a more "immune-hot" tumor microenvironment. Finally, dual blockade of the MNK1/2-eIF4E axis and the PD-1/PD-L1 checkpoint demonstrated efficacy in multiple pre-clinical mouse models of melanoma. Using MNK1/2 inhibitors to repress phospho-eIF4E thus offers a new strategy to inhibit melanoma plasticity and improve the efficacy of anti-PD-1 immunotherapy. Next, we investigated how reprogramming lipid metabolism mediates the response of melanoma cell states to MAPK-targeted therapies. We demonstrated that a subset of CD36+ melanoma persister cells tolerate MAPK inhibition through a unique mechanism in which peroxisomes and UGCG collaboratively mediate metabolic rewiring. Genetic inhibition of the peroxin PEX3 reduced peroxisome numbers and augmented MAPK inhibitor (MAPKi)-induced apoptosis in melanoma cells. Using lipidomic analysis, we showed that peroxisome deficiency sensitized melanomas to MAPKi through reprogrammed lipid metabolism, resulting in an increased reliance on UGCG-mediated ceramide metabolism for survival. Re-analysis of a single cell RNA-seq dataset revealed that, while MAPK inhibitors decreased the overall metabolic activity of patient-derived xenografts, a CD36+ cell subpopulation remained metabolically active during minimal residual disease and was characterized by the expression of UGCG and peroxisomal genes. Dual blockade of PEX3 and UGCG selectively eliminated CD36+ persister cells, thereby sensitizing melanoma to MAPKi and delaying resistance. Moreover, therapy-resistant melanomas were re-sensitized to MAPK-targeted therapy when PEX3 and UGCG were simultaneously inhibited. Finally, we combined a small molecule inhibitor that blocks PEX3-PEX19 interaction with a UGCG inhibitor, which led to reduced CD36+ persister cells and sensitized melanomas to MAPK inhibition. Together, our study supports a novel approach to potentiate melanoma response to MAPK-targeted therapies and overcome acquired resistance by disrupting peroxisome and UGCG-mediated lipid metabolism.In conclusion, our data highlight the growing appreciation of targeting translational control and metabolic reprogramming to modulate melanoma plasticity and therapeutic response. Inhibitors of mRNA translation and inhibitors of lipid metabolism, therefore, represent two promising therapeutic approaches to improve responses to standard of care therapies in melanoma"--
Download or read book Targeted Therapies in Breast Cancer written by Gw Sledge and published by Clinical Pub. This book was released on 2012-06 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new volume updates the reader on selected areas of targeted therapy in breast cancer, with special emphasis on chemoprevention strategies, drug resistance, biomarkers, combination chemotherapy, angiogenesis inhibition and pharmacogenomics in the context of clinical efficacy. This selected review of targeted therapies will guide the reader on effective treatment as part of an integrated programme of patient management.
Download or read book Immunotherapy of Hepatocellular Carcinoma written by Tim F. Greten and published by Springer. This book was released on 2018-08-22 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.
Download or read book Skin Cancer Pathogenesis and Diagnosis written by Ashish Dwivedi and published by Springer Nature. This book was released on 2021-08-02 with total page 251 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the molecular and cellular mechanisms involved in the initiation and progression of skin cancer. It also explains the role of the environment in skin cancer development and explores the potential of microbiome in the diagnosis, prevention and treatment of skin cancer. The book also presents potential biomarkers for early detection of skin cancer and discusses recent advances in skin cancer prevention and treatment using photodynamic therapy. Lastly, it summarizes the applications of biomedical engineering, non-coding and nanotechnology in the diagnosis and therapeutics in skin cancer. It is a valuable resource for investigators in the field of skin cancer, including pathologists, medical and surgical oncologists, and dermatologists.
Download or read book Handbook of Cancer Treatment Related Symptoms and Toxicities written by Vamsidhar Velcheti and published by Elsevier Health Sciences. This book was released on 2021-01-28 with total page 355 pages. Available in PDF, EPUB and Kindle. Book excerpt: Early recognition and management of adverse effects of cancer treatments are essential for optimal care of patients with cancer, and drastically different approaches are required for different physiologic reactions. Handbook of Cancer Treatment-Related Symptoms and Toxicities is a focused, one-stop resource that enables clinicians to quickly find up-to-date, reliable information needed at the point of care. The high-yield approach prioritizes the most common toxicities associated with cancer treatment, and concise, templated chapters offer fast access to information needed in day-to-day practice. Presents a user-friendly overview of cancer treatment-related symptoms and toxicities management in a practical, easy-to-use format, allowing you to quickly find information in one convenient, concise resource. Covers systemic and radiation therapies, including chemotherapy, immunotherapy, targeted therapies, and radiation therapy, detailing symptoms of each toxicity to confirm your diagnosis. Overviews pharmacologic and non-pharmacologic approaches to symptom management. Offers recommendations for mitigating toxicities in high-risk patients. Discusses key topics such as management of infusion reactions, when the need for biopsy is warranted, and the unique challenges posed by novel immunotherapies.
Download or read book Critical Issues in Head and Neck Oncology written by Jan B. Vermorken and published by Springer Nature. This book was released on 2023-03-27 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is an open access book. With a wealth of exciting data emerging in this rapidly evolving field this book will review the state-of-the-art knowledge with emphasis on multidisciplinary decision and management of head and neck cancer. The book provides significant detail on a wide range of topics including: the role of new targets for treatment, immunotherapy, resistance mechanisms, standardizing molecular profiling programs, and new methods to guide therapeutic approaches. In addition different disease situations are addressed including different treatment approaches in primary disease and in recurrent and/or metastatic disease as well as new developments in pathology, surgery and reconstruction techniques, new systemic therapies in salivary gland cancer, and supportive care and follow-up. All disciplines involved in the treatment of head & neck cancer are covered with a focus on translation into daily practice. The 8th-THNO is designed for medical oncologists, head and neck surgeons, radiation oncologists, otolaryngologists, and other medical professionals involved in the treatment of patients with head and neck cancer.
Download or read book Apoptosis and Cancer Chemotherapy written by John A. Hickman and published by Springer Science & Business Media. This book was released on 1999-04-08 with total page 347 pages. Available in PDF, EPUB and Kindle. Book excerpt: The past few years have witnessed an astonishing international effort that established the role of some 20 new molecules in apoptosis and added activation or suppression of apoptosis to the accepted biological functions of a great many others already familiar in cancer biology. Some of these molecules are receptors, transducing cytokine-mediated signals; others appear to intensify or diminish the risk that a compro mised cell will fire its apoptosis effector mechanism. All are of interest as potential targets for tumor therapy, and some may prove to be control points influenced in the pathogenesis of cancer and other diseases as diverse as viral infection, neurodegenerative disorders, and stroke. Sometimes, in the midst of these developments, a kind of euphoria ap pears to have gripped the research community, with the expectation that apoptosis will afford explanations to many unsolved questions in cellu lar regulation. This book, in a series of thoughtful and provocative ar ticles--some from established leaders in the field, and others from younger scientists--seeks to redress the balance.
Download or read book Cutaneous Melanoma written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Theranostic Approach for Pancreatic Cancer written by Ganji Purnachandra Nagaraju and published by Academic Press. This book was released on 2020-01-15 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: Theranostic Approach for Pancreatic Cancer modulates the biologic properties of stroma in pancreatic cancer by targeting the several chemotherapy resistance mechanisms to impede their malignant property through introducing new strategies and drugs for tackling the disease. It brings information about ongoing research as well as clinical data about pancreatic cancer and provides detailed descriptions about diagnostic and therapeutic options for easy understanding. This book discusses several topics related to pancreatic cancer such as stem cells, drug resistance and pancreatic tumor microenvironment, the latest developments in chemotherapy for metastatic cancer and chemoprevention, and epigenome as a therapeutic strategy. Additionally, it encompasses a discussion on theranostic clinical applications for personalized treatment and management of pancreatic cancer. The book is a valuable resource for cancer researchers, oncologists, and several members of the biomedical field who need to understand more about the diagnosis and treatment of pancreatic cancer. Provides information on the roadblocks of chemotherapy in patients with newly diagnosed and metastatic pancreatic cancer Discusses treatment options available currently as well as prospective options for the future Focuses especially on stroma, tumor microenvironment, stem cells, stellate cells, transcription factors, growth factors, and important signaling pathways as already tested types of treatment
Download or read book Chemo Radiation Resistance in Cancer Therapy written by Zhe-Sheng Chen and published by Frontiers Media SA. This book was released on 2022-06-06 with total page 393 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Advanced Healthcare Materials written by Ashutosh Tiwari and published by John Wiley & Sons. This book was released on 2014-05-09 with total page 421 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offers a comprehensive and interdisciplinary view of cutting-edge research on advanced materials for healthcare technology and applications Advanced healthcare materials are attracting strong interest in fundamental as well as applied medical science and technology. This book summarizes the current state of knowledge in the field of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, and up-and-coming bioengineering devices. Advanced Healthcare Materials highlights the key features that enable the design of stimuli-responsive smart nanoparticles, novel biomaterials, and nano/micro devices for either diagnosis or therapy, or both, called theranostics. It also presents the latest advancements in healthcare materials and medical technology. The senior researchers from global knowledge centers have written topics including: State-of-the-art of biomaterials for human health Micro- and nanoparticles and their application in biosensors The role of immunoassays Stimuli-responsive smart nanoparticles Diagnosis and treatment of cancer Advanced materials for biomedical application and drug delivery Nanoparticles for diagnosis and/or treatment of Alzheimers disease Hierarchical modelling of elastic behavior of human dental tissue Biodegradable porous hydrogels Hydrogels in tissue engineering, drug delivery, and wound care Modified natural zeolites Supramolecular hydrogels based on cyclodextrin poly(pseudo)rotaxane Polyhydroxyalkanoate-based biomaterials Biomimetic molecularly imprinted polymers
Download or read book Comparative Oncology written by Alecsandru Ioan Baba and published by . This book was released on 2007 with total page 787 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Recent Advances in the Biology Therapy and Management of Melanoma written by Lester Davids and published by BoD – Books on Demand. This book was released on 2013-02-13 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book Recent Advances in the Biology, Therapy and Management of Melanoma brings up-to-date information regarding a number of aspects which culminate in illuminating potential targets in the fight against melanoma. This book is intended to be a reference book for both the scientific and clinical communities and brings complicated subject matter together in an easy, readable way. Undoubtedly fundamental scientific understanding has to then be translated to the clinic in order for us to make significant strides in eradicating melanoma. It is hoped that scientists, clinicians, students and residents find this book useful in their studies on melanoma and that it not only expands their perspectives and views on the field, but challenges them to forge ahead towards discovering the ultimate cure.
Download or read book Targeted Therapies in Cancer written by Francesco Colotta and published by Springer Science & Business Media. This book was released on 2007-12-05 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: Billions of dollars are spent every year on research into targeted therapies for cancer. That’s why it’s more than ever crucial for the thousands of scientists working in the field to keep right up to date with the cutting edge. This fascinating collection of material goes a long way to helping them do so, featuring as it does contributions to a crucial international meeting in Italy. The meeting provided a forum for scientists and clinicians working in cancer drug discovery and therapy to share their opinions and experiences. The text here offers readers an overview of diverse approaches, ranging from drug discovery to cellular therapy. Overall, the book addresses the key question of whether ultimately targeted therapy in cancer will be a myth or a reality.
Download or read book Tertiary Lymphoid Structures written by Marie-Caroline Dieu-Nosjean and published by Humana Press. This book was released on 2018-09-05 with total page 289 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.
Download or read book Gene Therapy for Cancer written by Kelly K. Hunt and published by Springer Science & Business Media. This book was released on 2007-10-26 with total page 469 pages. Available in PDF, EPUB and Kindle. Book excerpt: The three sections of this volume present currently available cancer gene therapy techniques. Part I describes the various aspects of gene delivery. In Part II, the contributors discuss strategies and targets for the treatment of cancer. Finally, in Part III, experts discuss the difficulties inherent in bringing gene therapy treatment for cancer to the clinic. This book will prove valuable as the volume of preclinical and clinical data continues to increase.
Download or read book Manipulating the Immunological Tumor Microenvironment written by Peng Qu and published by Frontiers Media SA. This book was released on 2022-03-31 with total page 792 pages. Available in PDF, EPUB and Kindle. Book excerpt:
