This book represents an up-dated summary of the state of the art of the characterization of cancer stem cell/ cancer initiating cell (CSC/CIC) properties. An overview of the definition and biological properties of CSCs/CICs as well as the role of these cells in determining the resistance to standard and immune-based therapies is provided. It also discusses limitations in the achievement of a definitive biological characterization of CSCs/CICs due to their high extent of plasticity and heterogeneity that is also mutually driven by the interaction of these cells with the tumor microenvironment. The limitations in targeting CSCs/CICs with immunotherapy are also explained together with explorative combination approaches that could increase the susceptibility of these cells to the recognition by immune cells. This book is conceived for a broad audience, including students, teachers, scientific experts. The critical revision of available results in terms of immunological profile of CSCs/CICs and the efficacy in targeting these cells by immunological approaches, results in a comprehensive and up to date recapitulation of the field and provides interesting suggestions on how to focus future investigations in order to assess the role of CSCs/CICs as prognostic and predictive biomarkers of responsiveness to therapies for cancer patients.

Targeted therapies were initially developed to exploit the upregulation and dependence on key oncogenic pathways critical to cancer progression. Additionally, they also presented as a method to overcome chemoresistance by supplementing conventional therapeutic regimens with targeted therapies. However, the development of resistance to these combinatorial approaches has led to the reassessment of currently available therapeutic options to overcome resistance to targeted therapy. This book aims to provide an update on the advancements in the therapeutic arms race between cancer, clinicians and scientists alike to overcome resistance to targeted therapies. Subject experts provide a comprehensive overview of the challenges and solutions to resistance to several conventional targeted therapies in addition to providing a discussion on broad topics including targeting components of the tumor microenvironment, emerging therapeutic options, and novel areas to be explored concerning nanotechnology and the epigenome.

Targeted Therapy in Translational Cancer Research for the Translational Oncology series provides a comprehensive overview of recent developments in our understanding of tumor biology, elucidates the roles of targets and pathways involved in carcinogenesis, and describes current state-of-the-art anticancer therapy, as well as the most promising areas of translational research and targeted therapy. Introduces cutting-edge ‘bench to bedside and back’ breakthroughs which have transformed the diagnosis, prognosis, and treatment of cancer Covers basic principles of targeted therapy, including immunotherapy and the roles of cancer stem cells, the microenvironment, angiogenesis, epigenetics, microRNAs, and functional imaging in precision medicine Summarises major advances in therapeutic management of hematologic malignancies and solid tumors using conventional therapy, targeted therapy, immunotherapy, or novel treatment modalities

This reference book, which is the second volume of Targeting Oxidative Stress in Cancer, explores oxidative stress as the potential therapeutic target for cancer therapy. The initial chapters discuss the molecular mechanisms of oxidative stress and its effects on different signaling pathways. Subsequently, the sections examine the impact of redox signaling on tumor cell proliferation and consider the therapeutic potential of dietary phytochemicals and nutraceuticals in reactive oxygen species (ROS)-induced cancer. In turn, it examines the evidence supporting the use of Vitamin C in cancer management, before presenting various synthetic and natural compounds that have therapeutic implications for oxidative stress-induced cancer. It also explores the correlation between non-coding RNA and oxidative stress. Furthermore, the book summarizes the role of stem cells in ROS-induced cancer therapy and reviews the therapeutic applications of nanoparticles to alter redox haemostasis in cancer cells. Lastly, it explores heat-shock proteins, ubiquitin ligases, and probiotics as potential therapeutic agents in ROS-mediated cancer. This book is a useful resource for basic and translational scientists as well as clinicians interested in the field of oxidative stress and cancer therapy. ​

Cancer Stem Cells covers a wide range of topics in cancer stem cell biology, including the functional characteristics of cancer stem cells and how they're generated, where they are localized, the means by which cancer stem cells can be targeted, and how cancer stem cells can be reprogrammed back to normal tissue stem cells. Each chapter begins with a brief historical note and concept summary, followed by a description of the latest basic or clinical advance associated with the topic. Cancer Stem Cells builds systematically from coverage of the basic research stage to an advanced research level, from clinical relevance to therapeutic potential, and will be a valuable resource for professionals in the fields of cancer research and stem cell biology.

The “cancer stem cell” hypothesis postulates that cancer arises from a subpopulation of tumor-initiating cells or cancer stem cells (CSCs). While the idea of cancer stem cells has been around for more than a hundred years, evidence from the fields of hematology and cancer biology has now demonstrated the critical role of stem cells in hematological malignancies and suggested that these same mechanisms are also central to the initiation, progression, and treatment of solid cancers. Clinical and experimental studies have shown that CSCs exhibit many classical properties of normal stem cells, including a high self-renewal capacity and the ability to generate heterogeneous lineages; the requirement for a specific “niche”/microenvironment to grow; and an increased capacity for self-protection against harsh environments, toxins, and drugs. Cancer Stem Cells in Solid Tumors represents a detailed overview of cancer stem cells and their role in solid cancers. Comprised of 24 chapters, this volume will provide readers with a comprehensive understanding of this important and evolving field. Topics covered include: Introduction of the CSC hypothesis Historical perspectives and the contributing lessons from leukemia Current knowledge regarding the identification and role of CSCs in various forms of solid cancer including breast, brain, colorectal, pancreatic, prostate, melanoma, lung, ovarian, hepatocellular, and head and neck cancer Molecular pathways involved in driving CSC function, with a particular focus on the novel convergence of embryonic and tumorigenic signaling pathways In vitro and in vivo assays, model systems, and imaging modalities for studying CSCs The clinical importance of CSCs for cancer management and treatment, including important implications for prognosis, prediction, and treatment resistance Consideration of the controversy surrounding the CSC hypothesis and important unanswered questions in this field This collective work was written by a group of prominent international experts in cancer biology, oncology, and/or stem cell biology. It will serve as a valuable resource for established researchers, professors, health care professionals, and students in the medical and scientific community who are investigating stem cells and/or oncology.

Cancer Stem Cells and Signaling Pathways explores the mechanism of cancer stem cell signaling pathways in cancer advancement, serving as an ideal reference guide for investigators with valuable answers to problems associated with anti-cancer treatments and an understanding of the crosstalk among the signaling pathways in CSC regulation. Despite recent advances in tumor therapy and a greater understanding of their biology, tumors continue to be a prevalent and fatal worldwide. According to a novel paradigm in tumor biology, a small percentage of the cells within a tumor known as cancer stem cells (CSCs) are predicted as a crucial population for tumor progression. - Presents cancer stem characteristics and their signaling pathways - Highlights the use of animal models for cancer research, the use of genetically modified stem cells to deliver antitumor agents, and the significance of stem cell signaling in drug discovery - Covers basic and translational research appropriate for scientists and clinicians exploring alternative treatments for various cancers

Basic scientific background Breast cancer is one of the most common cancer and the most frequent cause of cancer death among women worldwide. Currently, subtyping breast cancers into hormone receptor (HR) positive, human epidermal growth factor receptor-2 overexpressing (HER2+), and triple negative breast cancer (TNBC) is the basis of diagnosing and treating this disease. The main treatment strategies for breast cancer include surgery, endocrine therapy, molecular targeted therapy, chemotherapy, radiotherapy, immunotherapy and gene therapy. However, resistance of breast cancer cells to chemotherapeutic agents, molecular targeted therapies and immunotherapy may occur either intrinsically or de nova, and is often ultimately responsible for treatment failure. Therefore, drug resistance poses a major challenge to breast cancer treatment. Current developments: Drug resistance in breast cancer is a complex clinical condition originating from a wide range of molecular alterations. The development of endocrine therapy resistance is believed to be associated with many cellular changes, such as ESR1 gene mutations, bypassing estrogen signaling pathway and altered tamoxifen metabolism. Meanwhile, changes in immune response, alternation of drug-binding property and downstream pathways are involved in the mechanisms of drug resistance in HER2+ breast cancer. In addition, resistance to chemotherapeutic agents predominantly arises from increased drug efflux and cross resistance. Current studies suggest that treatment strategies and therapeutics have to be designed specifically to each patient in different clinical situations. The use of modern genomic, proteomic and functional analytical techniques has contributed to identify novel genes and signaling networks involved in breast cancer drug resistance. Moreover, the use of high-throughput techniques in combination with bioinformatics and systems biology approaches has aided the interrogation of clinical samples and allowed the identification of molecular signatures and genotypes that predict responses to certain drugs. Despite much progress has been made in the field of breast cancer drug resistance, such as combination therapy and drug-loaded nanoparticles, the complexity and variability of drug resistance mechanism still inevitably lead to the continuous occurrence of drug resistance. Therefore, with the increasing amounts of anti-breast cancer agents, there are now unprecedented opportunities to understand and overcome drug resistance through further research into mechanisms and corresponding strategies, which will help achieve lasting disease control and bring survival benefits to patients with advanced cancer. Papers of interest: The current Research Topic of Frontiers in Pharmacology focuses on publishing Original Research, Review articles and Case Reports focusing on (a) elucidating mechanisms of drug resistance in breast cancer, target mutations, tumor microenvironment, undiscovered genes and signaling pathways; (b) promising drug delivery systems that can enhance the sensitivity of anti- breast cancer agents to various tumors; (c) strategies that can improve patient care during bio-chemotherapeutic treatments; (d) small molecule compounds that are effective against drug-resistant breast tumors (e) biomarkers of chemotherapy resistance in breast cancer patients and (f) in vitro and in vivo models. Guidelines for article of submission: - Authors must stick to the set guidelines for ethical practices by the Frontiers journals. - The main content of the article must have certain innovation and research significance. - The authors should describe the construction method of drug-resistant cell lines when using them for experiments in the article.

Although cancer development and progression depend on stochastic mutational events, the tumor has to be seen in the context of the host environment, and unraveling the environmental factors that support solid tumors is at the root of cancer prevention and cure. This Special Issue, focused on the dynamic crosstalk that occurs between tumor cells and the surrounding microenvironment and also including the cancer cells that represent a reservoir of self-sustaining cells for tumor maintenance, adds new knowledge about tumor–host interactions that is useful for novel diagnostic and therapeutic approaches.