Drug Resistance In Colorectal Cancer Molecular Mechanisms And Therapeutic Strategies

Author : Chi Hin Cho
Publisher : Academic Press
ISBN 13 : 0128199385
Total Pages : 242 pages
Book Rating : 4.81/5 ( download)

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Download or read book Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies written by Chi Hin Cho and published by Academic Press. This book was released on 2020-05-24 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies, Volume Eight, summarizes the molecular mechanisms of drug resistance in colorectal cancer, along with the most up-to-date therapeutic strategies available. The book discusses reasons why colorectal tumors become refractory during the progression of the disease, but also explains how drug resistance occurs during chemotherapy. In addition, users will find the current therapeutic strategies used by clinicians in their practice in treating colorectal cancer. The combination of conventional anticancer drugs with chemotherapy-sensitizing agents plays a pivotal role in improving the outcome of colorectal cancer patients, in particular those with drug-resistant cancer cells. From a clinical point-of-view, the content of this book provides clinicians with updated therapeutic strategies for a better choice of drugs for drug-resistant colorectal cancer patients. It will be a valuable source for cancer researchers, oncologists and several members of biomedical field who are dedicated to better treat patients with colorectal cancer. Presents a systemic summary of molecular mechanisms for a quick and in-depth understanding Updates current trends in the field with pioneering information on drug resistance Encompasses both basic and clinical approaches for a better understanding of unsolved problems from a holistic point-of-view

Author : Shilpa S. Dhar
Publisher : Frontiers Media SA
ISBN 13 : 2832506410
Total Pages : 201 pages
Book Rating : 4.17/5 ( download)

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Download or read book Molecular Mechanisms and Targeted Therapies for Colorectal Cancer written by Shilpa S. Dhar and published by Frontiers Media SA. This book was released on 2022-11-18 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author : Vibhuti Agrawal
Publisher :
ISBN 13 :
Total Pages : 181 pages
Book Rating : 4.11/5 ( download)

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Download or read book Dissecting the Molecular Mechanisms of Therapeutic Resistance in Cancer written by Vibhuti Agrawal and published by . This book was released on 2017 with total page 181 pages. Available in PDF, EPUB and Kindle. Book excerpt: Therapeutic resistance continues to be a persistent challenge in medical oncology. In clinical settings, resistance can occur at the beginning of treatment, or may be acquired after an initial clinical response to the therapy. Several mechanisms of drug resistance have been described in cancer, including alterations in the drug transport and metabolism process, mutations in drug-target, activation of bypass signaling pathways, inhibition of cell-death pathways, and induction of an epithelial to mesenchymal transition (EMT) in response to cytotoxic or targeted therapies. In this study, I have investigated the molecular mechanisms underlying ZEB 1-induced EMT and established a new computational framework that uses inter-animal heterogeneity to identify drivers responsible for variable phenotypic responses across different animals. EMT describes a cell-state switching process wherein epithelial cells lose their tight cell-cell junction contacts, and acquire the ability to migrate and invade the surrounding stroma to enter into blood circulation. Given the widespread role of EMT in drug resistance, it is imperative to identify therapeutic strategies to inhibit this transition. To identify druggable targets to block EMT progression, and therefore overcome EMT-mediated therapeutic resistance, I studied the effects of ZEB 1 expression on cellular signaling networks. By quantifying changes in tyrosine phosphorylation at different time points during ZEB 1-induced EMT, I found that Src family kinases (SFKs) were activated within 24 hours of ZEB 1 expression. Inhibition of SFKs blocked not only ZEB 1-induced EMT, but also EMT initiated by TGFp- and EGF signaling pathways in both breast and NSCLC cell-lines. SFK inhibition also prevented EGFR inhibitor-induced EMT and drug resistance in NSCLC cells both in vitro and in vivo. Mechanistically, SFK activation stabilized ZEBI by promoting ERK1/2-mediated phosphorylation on three serine residues, S583, S646, and S679. Consequently, MEK inhibition phenocopied the effects of blocking SFK activity with regards to decreasing stability of ZEB 1 and inhibiting ZEB 1-induced EMT. These results provide a new therapeutic application of SFK inhibitors as a potential anti-EMT therapy, to enhance the susceptibility of cancer cells to chemo- or targeted therapies. In the second part of this thesis, I have described a computational framework that leverages inter-animal heterogeneity to identify molecular mechanisms underlying variable phenotypic responses across different animals. Substantial inter-animal variability in phenotypes within the same treatment group, limits our ability to draw conclusions or gain meaningful insights about a biological process by simply averaging the data. To identify molecular drivers for heterogeneous phenotypic responses, I have established a method where each animal is considered as an individual entity whose phenotypic response is dependent on the state of its underlying signaling networks. As a proof of concept, I have used this method to successfully predict the resistance mechanisms of CDK4/6 inhibitor, palbocilib in two GBM PDX and one MPNST PDX models. The GBM6 model activated EGFR signaling upon treatment with palbociclib whereas the GBM22 and MPNST3 models activated SFKs and PDGFRa signaling in resistant tumors. Across all three PDX tumor models, treatment with combination therapies, consisting of palbociclib and an inhibitor targeting the activated bypass signaling pathway, substantially prolonged survival of mice. Thus, these results suggest that inter-animal variability can be used as a tool to predict drivers for a specific phenotypic response across different treatment conditions.

Author : Benjamin Bonavida
Publisher : Springer Science & Business Media
ISBN 13 : 1461470706
Total Pages : 271 pages
Book Rating : 4.00/5 ( download)

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Download or read book Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy written by Benjamin Bonavida and published by Springer Science & Business Media. This book was released on 2013-07-04 with total page 271 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​​​​​This volume gives the latest developments in on the mechanisms of cancer cell resistance to apoptotic stimuli, which eventually result in cancer progression and metastasis. One of the main challenges in cancer research is to develop new therapies to combat resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance to cytotoxic drug-induced apoptosis. These mechanisms should reveal gene products that directly regulate resistance in order to develop new drugs that target these resistance factors and such new drugs may either be selective or common to various cancers. If successful, new drugs may not be toxic and may be used effectively in combination with subtoxic conventional drugs to achieve synergy and to reverse tumor cell resistance. The research developments presented in this book can be translated to produce better clinical responses to resistant tumors.

Author : Sameer Ullah Khan
Publisher : Springer Nature
ISBN 13 : 9819716667
Total Pages : 392 pages
Book Rating : 4.61/5 ( download)

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Download or read book Drug Resistance in Cancer: Mechanisms and Strategies written by Sameer Ullah Khan and published by Springer Nature. This book was released on with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author : Jindong Chen
Publisher : BoD – Books on Demand
ISBN 13 : 1789231000
Total Pages : 130 pages
Book Rating : 4.07/5 ( download)

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Download or read book Colorectal Cancer written by Jindong Chen and published by BoD – Books on Demand. This book was released on 2018-05-16 with total page 130 pages. Available in PDF, EPUB and Kindle. Book excerpt: With international experts sharing their experience and knowledge on these different aspects in the management of colorectal cancer, this book has this opportunity to offer all physicians treating colorectal cancer, as well as researchers, updated information concerning the biology, diagnosis, screening, and treatment of colorectal carcinoma. This book provides a detailed evaluation of diagnostic modalities, in-depth analysis of screening for colorectal cancer, recent advances in treatment, and principles and trends in the management of colorectal cancer. This updated knowledge will be an interesting and informative read for any clinician involved in the management of patients with colorectal cancer. In addition, readers such as related physicians, researchers, and colorectal cancer patients are potential beneficiaries of this book.

Author : Ganji Seeta Rama Raju
Publisher : Springer Nature
ISBN 13 : 9811520178
Total Pages : 261 pages
Book Rating : 4.74/5 ( download)

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Download or read book Theranostics Approaches to Gastric and Colon Cancer written by Ganji Seeta Rama Raju and published by Springer Nature. This book was released on 2020-03-04 with total page 261 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the importance of understanding gastric and colon cancer metabolism in guiding diagnosis and drug discovery. It summarizes the correlation between adiponectin and matrix metalloproteinase with colorectal cancer. The book also evaluates the divergent role of hypoxia-inducible factor 1 in colorectal cancer growth and metastasis. After discussing the role of genetic polymorphisms in alcohol metabolizing enzymes and EPHX1 with the onset of colorectal cancer, it reviews the molecular mechanisms of chemoresistance in gastric cancer and novel therapeutic strategies to reverse the chemoresistance of tumors. In addition, the book explores the theranostic role of nanoparticles and therapeutic potential of phytochemicals with regard to colorectal cancer. Given its scope, the book offers a valuable guide for oncologists, academic researchers, pharmaceuticals practitioners, and students who are involved in research and treatment of cancer.

Author : Rishabha Malviya
Publisher : John Wiley & Sons
ISBN 13 : 1394209843
Total Pages : 228 pages
Book Rating : 4.42/5 ( download)

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Download or read book Multi-Drug Resistance in Cancer written by Rishabha Malviya and published by John Wiley & Sons. This book was released on 2023-07-18 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: MULTI-DRUG RESISTANCE IN CANCER The book details the mechanisms underlying multi-drug cellular resistance and the targets of novel chemotherapeutic agents. Cancer is a major killer all over the world. Even with all the progress made, chemotherapy is still the mainstay of modern cancer treatment. The progression of the cellular defeat of numerous independent anticancer drugs in terms of their chemical structure is a major barrier to successful chemotherapy. Multi-drug resistance (MDR) is a term for the fact that most cancer patients exhibit this phenomenon. According to the numbers, drug resistance carries the blame for 90% of cancer patient deaths. Refractory cancer and tumor recurrence are common outcomes of prolonged chemotherapy. Because of the prevalence of drug-resistance mutations, the difficulty of treating tumors increases and the therapeutic efficacy of drugs decreases. Multi-Drug Resistance in Cancer: Mechanism and Treatment Strategies contains nine chapters that cover topics such as: studying the mechanics of resistance to drugs by autophagy; studies to delineate the role of efflux transporters; expression of drug transporters; resistance to targeted therapies in breast cancer; advances in metallodrug driven combination treatment for cancer; and use of natural agents for the overcoming of cancer drug resistance. The book aims to provide the latest data on the mechanisms of cellular resistance to anticancer agents currently used in clinical treatment. It provides a better understanding of the mechanisms of MDR and targets of novel chemotherapy agents which should guide future research concerning new effective strategies in cancer treatment. Audience This book is written for pharmaceutical and biomedical scientists and researchers at both the bench and in the clinic who are interested in the mechanisms and strategies for overcoming cancer’s multi-drug resistance.

Author : Xiaofang Che
Publisher : Frontiers Media SA
ISBN 13 : 2832526101
Total Pages : 212 pages
Book Rating : 4.01/5 ( download)

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Download or read book Gastrointestinal Cancer Immunotherapy: from Drug Resistance Mechanisms to Overcoming Strategies written by Xiaofang Che and published by Frontiers Media SA. This book was released on 2023-06-15 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gastrointestinal (GI) cancers, including gastric cancer, colon cancer, liver cancer, esophageal cancer, and pancreatic cancer, seriously threaten the health of human beings worldwide with a high rate of morbidity and mortality. The clinical successes achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4 have opened a new cancer therapy era and brought new hope to cancer patients. However, the overall response rate (ORR) of ICI monotherapy in the non-selective population is only about 20%, in which some patients subsequently develop immunotherapy resistance. Moreover, the remaining 70-80% of patients displayed primary resistance to ICIs, and a few patients even experienced hyper progression disease (HPD). Although PD-L1 expression, mismatch repair deficient (MMRd), high tumor mutational burden (TMB-H) , high homologous recombination deficiency (HRD), and tumor infiltrated immune cells (TILs) are known as effective biomarkers for immunotherapy, growing studies have reported that ICIs could not improve the OS of all patients with PD-L1 expression higher than 50%, and the ORR of MSI-H patients was only about 60%, whereas some patients with low PD-L1 expression or MSS could still benefit from immunotherapy, indicating the complexity of ICI resistance. Therefore, it is of great importance and significance to explore the prediction biomarkers for primary or acquired immunotherapy resistance and elucidate their underlying molecular mechanisms and develop reversal strategies. Due to the multiple steps of the cancer immune cycle and complex immune microenvironment, any disorders of immune cell infiltration or T cell activation, such as lack of antigens and/or their presentation, lack of response to antigen presentation, and T cell priming, could contribute to ICI resistance. The combination with anti-angiogenesis therapy, radiotherapy, chemotherapy, and other ICIs has improved the efficacy of ICI therapy to some extent in the clinic. Although numerous studies related to ICI resistance were reported in GI cancers, due to the strong spatial/temporal heterogeneity and the complex immune microenvironment in different kinds of GI cancers and different individuals, many questions about ICI resistance and reversal strategies remain unsolved. The aim of this Research Topic is to provide a forum to exhibit the latest research achievement related to the exploration of biomarkers for immunotherapy resistance including HPD and the underlying molecular mechanisms, as well as the development of reversal strategies in GI cancers. We hope this Research Topic will lead to a better understanding of precision cancer immunotherapy and provide useful clues for clinical application to benefit more GI cancer patients with immunotherapy.

Author : Jun Zhou
Publisher : Humana Press
ISBN 13 : 9781617796647
Total Pages : 492 pages
Book Rating : 4.46/5 ( download)

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Download or read book Multi-Drug Resistance in Cancer written by Jun Zhou and published by Humana Press. This book was released on 2012-08-09 with total page 492 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .