Download or read book Targeting Breast Cancer Transcription driven Signaling Pathways to Improve Therapeutic Response in Triple Negative Breast Cancer written by Melyssa Susann Roberts and published by . This book was released on 2020 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Effective treatment for patients with triple negative breast cancer (TNBC) is highly limited by resistance and low treatment response rates. Though extensive research has been conducted to determine molecular mechanisms behind these obstacles, we still have limited understanding of their root causes. It is critical to identify proteins that regulate resistance in order to target these specific drivers that promote cellular reprogramming and cause the notable lack of response of TNBC. This would facilitate the development of improved therapeutic options that would ultimately improve patient survival outcomes. We discovered that expression of LIN9, a mitotic regulator, is required for the maintenance of taxane resistance. LIN9 inhibition, genetically or pharmacologically, restored taxane sensitivity, promoted mitotic progression errors, and led to cell death. However, LIN9 is a scaffolding protein that is not readily druggable, thus we identified a downstream target, NEK2 (NIMA-related Kinase 2) for which there are available inhibitors. We found that NEK2 expression is also required for taxane resistance and that its silencing both restores sensitivity and causes aberrant mitosis. Combination treatment with paclitaxel and a NEK2 inhibitor in vivo caused a significant decrease in tumor volume compared to either drug alone in both sensitive and resistant mouse models. Thus, the LIN9/NEK2 pathway is a driver of taxane resistance that can be therapeutically targeted to reverse resistance. We also discovered the transcription factor and metastasis suppressor KLF4 to be a key mediator of erlotinib response in TNBC cells. Erlotinib is an FDA-approved inhibitor of EGFR, a receptor that mediates a variety of tumorigenic signaling. As EGFR inhibitors have not been highly successful in the clinic, we sought to understand molecular reasons for this lack of response. We discovered that KLF4 inhibits EGFR expression and activity and that its expression increases response to erlotinib. This suggests KLF4 is a key regulator of drug response in TNBC through regulation of EGFR. Lastly, we transitioned our focus of breast cancer mortality from the laboratory bench to populations at risk. We assessed disparities in breast cancer mortality among women that vary with residence at diagnosis between Ohio urban and rural counties. We found that women who reside in rural counties have higher rates of breast cancer mortality than those in urban counties, controlling for age, stage at diagnosis, and race. Many risk factors pose challenges to those in rural areas including unhealthy lifestyles, limited access to healthcare providers, and poverty. This study identified an increased risk of breast cancer mortality in rural counties of Ohio, supporting the need to reduce the level of this disparity. Together, these studies identify critical driver pathways of drug response and resistance that could potentially be targeted in TNBC to improve patient outcomes, as well as identifying specific patient populations that have increased mortality risks.

Download or read book Therapeutic Drug Targets and Phytomedicine For Triple Negative Breast Cancer written by Acharya Balkrishna and published by Bentham Science Publishers. This book was released on 2023-01-13 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: Triple negative breast cancers (TNBC) are a biologically aggressiveform of breast cancer and constitute approximately 10-15% of all breast cancerpatients. Distant metastasis, lack of clinically targeted therapies andprognostic markers, makes the disease difficult to treat. Till now not muchwork has been carried out on this deadly disease. This book provides an overview of TNBC etiology, its treatmentstrategies and prognostic markers to identify the outcome of standard therapies.Signalling pathways namely cell proliferation, angiogenesis, invasion andmetastasis, apoptosis, autophagy and others involved in complicating thedisease have been described in the chapters to convey an understanding aboutthe disease mechanisms. All the possible drugs either in pre-clinical orclinical stages have also been mentioned with data that depicts their efficiencyin targeting altered genes. The book also introduces the reader to herbalmedicine exhibiting high potency to target TNBC, their synthetic analogs usedduring chemotherapy and their ability to fight against chemoresistance. Theconcept of phytonanotechnology has also been discussed. The book helps createawareness among a broad range of readers about TNBC. It points to prioritizingthe upgradation of health care facilities and re-designing future treatmentstrategies to provide maximum benefit to breast cancer patients.

Download or read book Overcoming Breast Cancer Therapy Resistance written by Zodwa Dlamini and published by Springer Nature. This book was released on with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Mechanisms of Drug Resistance And Strategies of Sensitization in Breast Cancer 2nd edition written by Yan Cheng and published by Frontiers Media SA. This book was released on 2024-01-11 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Epithelial Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.

Download or read book Computational driven Understanding of the Regulatory Mechanisms of the Breast Cancer Transcriptome and Its Implications for Drug Treatment written by Shujun Huang and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer (BC) is the most commonly diagnosed cancer and the major cause of cancer mortality among women worldwide. As a heterogenous disease, BC can be divided into four major molecular subtypes: luminal A, luminal B, HER2-enriched, and triple negative breast cancer (TNBC). The TNBC subtype shows the shortest survival time among the four groups and lacks effective targeted therapeutic strategies. Different BC subtypes display different transcriptome profiles. However, the dysregulated pathways and transcriptional regulators underlying the gene expression profiles of different BC subtypes have yet to be fully elucidated. Current research is investigating the dysregulated genes in BC with the aim to identify potential gene targets for BC while overlooking the fact these genes are often part of a pathway. Moreover, among the multi-omics data, gene expression profiles have been shown to be the most informative data for developing anti-cancer drug response prediction models in silico. But these models typically were developed with individual genes. Therefore, this thesis aimed to explore the breast cancer transcriptome with a focus on the TNBC subtype to address three major questions: 1) exploring the regulatory mechanisms driving the unique expression pattern of different BC subtypes; 2) identifying compounds that could affect the expression pattern of the top dysregulated pathways in BC; and 3) developing a drug response prediction model by using BC pathway activity profiles inferred from the transcriptome profiles. To address the first question, we collected the multi-omics data of BC samples from The Cancer Genome Atlas (TCGA) dataset, including gene expression, DNA methylation, copy number variation (CNV) and microRNA (miRNA) profiles, the transcription factor (TF)-binding data from TRRUST v2.0, and the miRNA-binding data from starBase v3.0. Using these data, the Lasso regression-based integrative analysis identified 25, 20, 15 and 24 key regulators for luminal A, luminal B, HER2-enriched and TNBC subtypes, respectively. A further look at the TNBC regulators found that many of them are regulating the FOXM1 (i.e., PID_FOXM1_PATHWAY) and PPARA (i.e., BIOCARTA_PPARA_PATHWAY) pathways. To address the second question, we focused on the FOXM1 and PPARA pathways. Using the Connectivity Map (CMAP) database, which provides drug-induced gene expression changes in MCF7 cell lines, we investigated how different compounds change the activity and expression pattern of the two pathways. Nineteen drugs (such as 5109870, MG-132, MG-262, celastrol, resveratrol, and cephaeline) were identified to decrease the FOXM1 pathway activity scores and reverse the FOXM1 pathway expression pattern while 13 drugs (such as cephaeline, pararosaniline, cycloheximide, monensin, wortmannin, and raloxifene) were identified to increase the PPARA pathway activity scores and reverse the PPARA pathway expression pattern. It may be of interest to validate these compounds experimentally. To address the third question, we collected the baseline gene expression profiles of 49 BC cell lines along with IC50 values of these cell lines to 220 drugs from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset. Using these data, we developed a multiple-layer cell line-drug response network (ML-CDN2) by integrating a one-layer cell line similarity network based on the pathway activity profiles and a three-layer drug similarity network based on three types of drug information. ML-CDN2 demonstrated good prediction performance, with the Pearson correlation coefficient between the observed and predicted IC50 values for all cell line-drug pairs of 0.873. Moreover, the ML-CDN2 model could be used to predict the drug response for new BC cell line samples or new BC patient-derived samples. This thesis demonstrated the transcriptional regulators underlying the transcriptome profiles in different BC subtypes. Moreover, this thesis demonstrated the implications of the BC transcriptome in drug treatment by identifying the drugs to modulate the two dysregulated pathways in BC and developing the anti-cancer drug response prediction model for BC by incorporating the transcriptome profiles.

Download or read book Drug and Therapy Development for Triple Negative Breast Cancer written by Pravin Kendrekar and published by John Wiley & Sons. This book was released on 2023-06-08 with total page 325 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug and Therapy Development for Triple Negative Breast Cancer The first comprehensive and up-to-date compilation of modern diagnostic and treatment methods for triple negative breast cancer In Drug and Therapy Development for Triple Negative Breast Cancer, a team of distinguished practitioners delivers an in-depth and authoritative discussion of contemporary methods for treating triple negative breast cancer (TNBC). The editors have included material that covers its molecular causes, initial detection, diagnostic tools, treatment procedures, pharmacology, and new and experimental therapies—including nanotherapeutics and photothermal therapies. As the first comprehensive compilation of modern treatment methods for TNBC, this reference is an unmatched source of information about current and future treatment approaches, including machine learning methods for earlier detection and more accurate diagnosis. Readers will also find: A thorough introduction to HER receptors in breast cancers Comprehensive explorations of the etiology and therapy of hormone receptor-positive breast cancer and the early-stage diagnosis of breast cancer Application of artificial intelligence to breast cancer diagnosis New insights on the role of DNA replication stress and genome instability in breast cancer Perfect for medicinal and pharmaceutical chemists, Drug and Therapy Development for Triple Negative Breast Cancer will also benefit oncologists and professionals working in the pharmaceutical industry or in hospital settings.

Download or read book Handbook of Targeted Cancer Therapy and Immunotherapy Breast Cancer written by Senthil Damodaran and published by Lippincott Williams & Wilkins. This book was released on 2022-06-07 with total page 612 pages. Available in PDF, EPUB and Kindle. Book excerpt: Designed for quick, everyday reference, Handbook of Targeted Cancer Therapy and Immunotherapy: Breast Cancer provides a practical overview of this rapidly advancing field. Comprehensive yet concise, this easy-access resource by Drs. Senthil Damodaran and Debu Tripathy of MD Anderson Cancer Center helps you filter and apply the most recent discoveries as they pertain to specific tumor types, actionable molecular targets, and clinical performance of approved or investigational targeted agents and combinations of agents.

Download or read book From Bedside to Bench written by Tia Hara Turner and published by . This book was released on 2020 with total page 192 pages. Available in PDF, EPUB and Kindle. Book excerpt: Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites of metastasis is crucial for developing effective treatment strategies. Given the molecular heterogeneity of TNBC, the clinical success of new therapies additionally depends on the identification of reliable drug targets within each TNBC subtype for more effective patient stratification. The studies presented herein sought to address these matters, using clinically relevant patient-derived xenograft (PDX) models to characterize chemotherapeutic efficacy in distinct metastatic sites, to identify promising targeted therapeutic candidates and combination strategies, and to assess the translational potential of these therapeutic strategies, with a focus on both the basal-like and luminal androgen receptor (LAR) subtypes of TNBC. We hypothesized that therapeutic efficacy in the primary tumor setting would be maintained in the metastatic setting, and that PDXs of distinct TNBC subtypes would respond to particular targeted therapies based on the distinct molecular pathways that drive their progression. We therefore expected that therapies targeting the epidermal growth factor receptor (EGFR) and the androgen receptor (AR) would have efficacy in basal-like TNBC and LAR TNBC, respectively, and would be ideal for incorporation into novel combination regimens for these specific disease subtypes. Using a combination of in vitro and in vivo drug response studies, we identified a drug combination, co-targeting EGFR and survivin, that was synergistic across multiple PDX models of basal-like TNBC, despite some of these models responding differently to standard chemotherapies, thus revealing potential pathways that may serve as reliable drug targets in this subset of patients. Furthermore, we identified several potential drug targets and therapeutic candidates for combination with AR-targeted therapies in LAR TNBC. In addition to identifying novel therapeutic strategies that have potential to provide clinical benefit for these subsets of TNBC patients, these studies highlight the utility of PDX models for in vitro and in vivo drug development studies, and demonstrate that the molecular and drug response profiles of primary tumors are maintained in the metastatic setting, indicating that studies employing PDX mammary tumor models can be applicable in advanced disease. Collectively, the data generated in these studies have the potential not only to directly provide clinical benefit for TNBC patients, but also to inspire and inform countless future research endeavors seeking to improve the therapeutic landscape in breast cancer.

Download or read book Combinational Therapy in Triple Negative Breast Cancer written by Manzoor Ahmad Mir and published by Academic Press. This book was released on 2022-04-28 with total page 262 pages. Available in PDF, EPUB and Kindle. Book excerpt: Combinational Therapy in Triple Negative Breast Cancer discusses TNBC at the molecular level from a holistic approach, focusing on combinational strategies targeting various pathways involved in this specific cancer type. Using a monotherapy for the treatment of cancer, especially high-grade tumors like TNBC, is mostly worthless due to the inherent genetic instability of tumor cells to develop intrinsic and acquired resistance. Combination therapy presents more, or at least the same, effectiveness with lower doses of every single agent and decreases the likelihood of chemoresistance, making it essential to understand for multiple therapy options. The book is a valuable resource for cancer researchers, oncologists, graduate students and members of the biomedical field who are interested in the potential of combinational therapies to treat triple negative breast cancer. Presents up-to-date and cutting-edge knowledge of Triple negative breast cancer (TNBC) biology, clinical aspects and treatment options Discusses novel targets and pathways involved in TNBC Provides insights and approaches for future research on TNBC

Download or read book Resistance to Targeted Therapies in Breast Cancer written by Jenifer R. Prosperi and published by Springer. This book was released on 2017-12-04 with total page 193 pages. Available in PDF, EPUB and Kindle. Book excerpt: We present an in-depth description of resistance to targeted therapies in breast cancer. Targeted therapies discussed here include those used to treat ER+ or Her2+ breast cancers (i.e., Tamoxifen or trastuzumab) or those targeting signaling pathways aberrantly activated in triple negative breast cancer (i.e., EGFR and Wnt signaling). We have also provided an overview of standard of care as an introduction into the importance of targeted therapy. It is our hope that this volume gives an insight into the landscape of breast cancer treatment, the challenges of targeted therapy, and a glimpse into the future of breast cancer therapy.

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 Studies of Improving Therapeutic Outcomes of Breast Cancer Through Development of Personalized Treatments and Characterization of Gene Interactions written by Jing-Ru Jhan and published by . This book was released on 2016 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Translational Research in Breast Cancer written by Erwei Song and published by Springer. This book was released on 2017-12-28 with total page 418 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a comprehensive introduction to translational efforts in breast cancer, addressing the latest approaches to precision medicine based on the current state of understanding of breast cancer. With the latest developments in breast cancer research, our understanding of the genomic changes and the oncogenic signaling cascade of breast cancer has made considerable strides. Further, the immuno-environment has been demonstrated as the barrier to clinical cancer. In addition, major advances in cancer biology, immunology, genomics and metabolism have broken new ground for designing therapeutic approaches and selecting appropriate treatments on the basis of more precise information on the individual patient. As a result of these two trends, a clearer picture of the molecular landscape of breast cancers has facilitated the development of diagnostic, prognostic and predictive biomarkers for clinical oncology. All these aspects are addressed in this volume, which offers a comprehensive resource for researchers, graduate students and oncologists in cancer research.

Download or read book Targeting New Pathways and Cell Death in Breast Cancer written by Rebecca Aft and published by BoD – Books on Demand. This book was released on 2012-02-29 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents novel in interesting find by multiple accomplished investigators in breast cancer. These chapters elucidate new mechanisms of breast cancer cell death as well as discuss new pathways for therapeutic targeting.

Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Download or read book Targeting Breast Cancer And Signaling Pathways By Crab Hormone Methyl Farnesoate written by Jyothsna Kancharla and published by . This book was released on 2023-01-16 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is a leading cause of cancer-related deaths among women worldwide. Methyl farnesoate (MF) is a natural compound that is found in crustaceans such as crab and is known to have anti-cancer properties. Studies have shown that MF can target breast cancer cells by inhibiting the growth and proliferation of these cells. MF has been found to target several signaling pathways that are known to play a role in the development of breast cancer. One of the pathways targeted by MF is the MAPK/ERK pathway, which is involved in cell proliferation, differentiation, and survival. MF has been found to inhibit the activity of this pathway, leading to the inhibition of cell growth and proliferation. Another pathway targeted by MF is the PI3K/Akt pathway, which is also involved in cell proliferation, differentiation, and survival. MF has been found to inhibit the activity of this pathway, leading to the inhibition of cell growth and proliferation. In addition, MF has also been found to target the Wnt/β-catenin signaling pathway, which is involved in cell proliferation and differentiation. MF has been found to inhibit the activity of this pathway, leading to the inhibition of cell growth and proliferation. Overall, MF has shown to be a promising compound for the targeting of breast cancer, by inhibiting several signaling pathways which are known to be involved in the development and progression of the disease. Further studies are needed to understand the underlying mechanisms of MF and to determine its potential as a therapeutic agent for breast cancer. Breast cancer (BC) is one of the world's leading causes of cancer-associated mortalities. According to GLOBOCAN, 2.1 million females were diagnosed with BC in 2018, accounting for 11.6 % of total cancer patients. As per this report, BC is nearly 1 in 4 cancer cases amongst women. The frequency of new cases of BC is raising in the majority of countries. Worldwide, the incidence of BC ranked one among the women cancers (Siegel et al., 2020). The prevalence rate of BC is very high in both transitioned and transitioning countries compared to other cancers due to risk factors associated with menstruation, reproduction, intake of hormones, nutrition, and anthropometry, postponement of childbearing, etc. Also, the prevalence rate of BC is rising in successive generations of high-risk populations. The characterization of pathophysiology and treatment of BC is highly challenging due to heterogeneous nature. They have rapid visceral as well as distant metastatic ability. Even some subtypes of BCs are highly aggressive and have unique proliferation markers, endocrine receptors, and epidermal growth factor receptors. They differ in cellular growth, mRNA translation energy metabolism and cell-cell communication.