Drug Resistance In Breast Cancer Mechanisms And Approaches To Overcome Chemoresistance

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.

Leading experts summarize and synthesize the latest discoveries concerning the changes that occur in tumor cells as they develop resistance to anticancer drugs, and suggest new approaches to preventing and overcoming it. The authors review physiological resistance based upon tumor architecture, cellular resistance based on drug transport, epigenetic changes that neutralize or bypass drug cytotoxicity, and genetic changes that alter drug target molecules by decreasing or eliminating drug binding and efficacy. Highlights include new insights into resistance to antiangiogenic therapies, oncogenes and tumor suppressor genes in therapeutic resistance, cancer stem cells, and the development of more effective therapies. There are also new findings on tumor immune escape mechanisms, gene amplification in drug resistance, the molecular determinants of multidrug resistance, and resistance to taxanes and Herceptin.

Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance, Volume 12, discusses new approaches that are being undertaken to counteract tumor plasticity, understand and tackle the interactions with the microenvironment, and disrupt the rewiring of malignant cells or bypass biological mechanism of resistance by using targeted radionuclide therapies. This book provides a unique opportunity to the reader to understand the fundamental causes of drug resistance and how different approaches are applied. It is a one-stop-shop to understand why it is so difficult to treat cancer, and why only a very few patients respond to therapy and a significant portion develop resistance. Despite a rapid development of more effective anti-cancer drugs and combination therapies, cancer remains the leading cause of lethality in the developed world. The main reason for this is the ability of heterogeneous subpopulations of tumor cells interacting with constantly evolving tumor microenvironment to resist elimination and eventually, trigger cancer relapse. In this book, experts review current concepts explaining molecular and biological mechanisms of cancer drug resistance and discussing advancing approaches for overcoming these therapeutic challenges. Provides the most updated knowledge on the mechanisms of cancer drug resistance and the emerging therapeutic approaches reviewed by experts in the field Brings detailed analyses of most important recently reported developments related to drug resistance and their relevance to overcoming it in cancer patients Discusses in-depth molecular mechanisms and novel concepts of cancer resistance to conventional and advanced therapies

One of the main causes of failure in the treatment of cancer is the development of drug resistance by the cancer cells. The design of cancer chemotherapy has become increasingly sophisticated, yet there is no cancer treatment that is 100% effective against disseminated cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumours, even those from the same tissue of origin. Frequently resistance is intrinsic to the cancer, but as therapy becomes more and more effective, acquired resistance has also become common. The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anticancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance. Studies on mechanisms of cancer drug resistance have yielded important information about how to circumvent this resistance to improve cancer chemotherapy and have implications for pharmacokinetics of many commonly used drugs. This book presents new and important research in this field.

​​​​​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.

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.