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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.
Book Synopsis Drug and Therapy Development for Triple Negative Breast Cancer by : Pravin Kendrekar
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.
Despite recent advances in adjuvant therapies of cancer, the regi mens of postoperative adjuvant chemotherapy treatment which are presently available fail to cure the majority of cancer patients. Pre operative (neoadjuvant) chemotherapy represents a new approach in drug scheduling, based on sound theoretical, pharmacokinetic, and experimental principles. The preoperative timing of chemotherapy before definitive sur gery is not a minor change in the therapy of cancer. To be successful, large numbers of practitioners and their patients must participate. Substantial alterations of many aspects of the present management of cancer will have to follow. Therefore, before such therapy can be fully and routinely implemented, results of the novel treatment and its rationale have to be carefully evaluated. In preoperative treatment, other features will likely gain impor tance. For the first time, clinicians have a chance to follow the in vivo response of the tumor exposed to preoperative chemotherapy. The subsequent histological assessment of the tumor sample may likely become an important prognostic guide, permitting more re fined individual approaches to the planning of postoperative adju vant treatment. The value of such a treatment strategy can already be appreciated in the clinical setting, as seen from the therapy of osteosarcoma. Furthermore, preoperative chemotherapy might render previously inoperable tumors operable and hence resectable with a curative intention. The preoperative reduction of tumor bulk may also effectively decrease the need for more radical operations, permitting a more uniform adoption of conservative surgery.
Book Synopsis Preoperative (Neoadjuvant) Chemotherapy by : Joseph Ragaz
Download or read book Preoperative (Neoadjuvant) Chemotherapy written by Joseph Ragaz and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 172 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite recent advances in adjuvant therapies of cancer, the regi mens of postoperative adjuvant chemotherapy treatment which are presently available fail to cure the majority of cancer patients. Pre operative (neoadjuvant) chemotherapy represents a new approach in drug scheduling, based on sound theoretical, pharmacokinetic, and experimental principles. The preoperative timing of chemotherapy before definitive sur gery is not a minor change in the therapy of cancer. To be successful, large numbers of practitioners and their patients must participate. Substantial alterations of many aspects of the present management of cancer will have to follow. Therefore, before such therapy can be fully and routinely implemented, results of the novel treatment and its rationale have to be carefully evaluated. In preoperative treatment, other features will likely gain impor tance. For the first time, clinicians have a chance to follow the in vivo response of the tumor exposed to preoperative chemotherapy. The subsequent histological assessment of the tumor sample may likely become an important prognostic guide, permitting more re fined individual approaches to the planning of postoperative adju vant treatment. The value of such a treatment strategy can already be appreciated in the clinical setting, as seen from the therapy of osteosarcoma. Furthermore, preoperative chemotherapy might render previously inoperable tumors operable and hence resectable with a curative intention. The preoperative reduction of tumor bulk may also effectively decrease the need for more radical operations, permitting a more uniform adoption of conservative surgery.
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.
Book Synopsis Therapeutic Drug Targets and Phytomedicine For Triple Negative Breast Cancer by : Acharya Balkrishna
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.
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.
Book Synopsis Targeted Therapies in Breast Cancer by : Gw Sledge
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.
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.
Book Synopsis Drug and Therapy Development for Triple Negative Breast Cancer by : Pravin Kendrekar
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 2023-06-27 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.
Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.
Book Synopsis Breast Cancer Metastasis and Drug Resistance by : Aamir Ahmad
Download or read book Breast Cancer Metastasis and Drug Resistance written by Aamir Ahmad and published by Springer Nature. This book was released on 2019-08-27 with total page 427 pages. Available in PDF, EPUB and Kindle. Book excerpt: Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.
This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoeconomics, and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.
Book Synopsis Metronomic Chemotherapy by : Guido Bocci
Download or read book Metronomic Chemotherapy written by Guido Bocci and published by Springer. This book was released on 2014-09-04 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoeconomics, and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.
In summary, this dissertation describes the development of three novel nanoparticles that can treat TNBC through distinct mechanisms: photothermal therapy, targeted drug delivery, and targeted miRNA replacement therapy. Future directions for this research are summarized in Chapter 6. With continued development and implementation, each of these nanoparticle formulations has great potential to improve patient outcomes.
Book Synopsis Treating Triple-negative Breast Cancer Through Nanoparticle-mediated Photothermal Therapy and Gene Regulation by : Danielle M. Valcourt
Download or read book Treating Triple-negative Breast Cancer Through Nanoparticle-mediated Photothermal Therapy and Gene Regulation written by Danielle M. Valcourt and published by . This book was released on 2020 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: In summary, this dissertation describes the development of three novel nanoparticles that can treat TNBC through distinct mechanisms: photothermal therapy, targeted drug delivery, and targeted miRNA replacement therapy. Future directions for this research are summarized in Chapter 6. With continued development and implementation, each of these nanoparticle formulations has great potential to improve patient outcomes.
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.
Book Synopsis Molecular Mechanisms of Drug Resistance And Strategies of Sensitization in Breast Cancer, 2nd edition by : Yan Cheng
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.
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.
Book Synopsis From Bedside to Bench by : Tia Hara Turner
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.
