Combinational Therapy in Triple Negative Breast Cancer

Combinational Therapy in Triple Negative Breast Cancer
Author: Manzoor Ahmad Mir
Publisher: Academic Press
Total Pages: 262
Release: 2022-04-28
Genre: Science
ISBN: 0323961371

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

Metronomic Chemotherapy

Metronomic Chemotherapy
Author: Guido Bocci
Publisher: Springer
Total Pages: 302
Release: 2014-09-04
Genre: Medical
ISBN: 3662436043

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.

Targeted Combination Therapy of Triple-negative Breast Cancer

Targeted Combination Therapy of Triple-negative Breast Cancer
Author: Ketki Bhise
Publisher:
Total Pages: 148
Release: 2021
Genre: Molecular biology
ISBN:

We tested the efficacies of three immune checkpoint inhibitors, namely blockades for CD73, CTLA4 and PD-L1 in combination with LipoDoxAtz to assess reduction in tumor growth. Owing to the possibility that antiPD-L1 and antiCTLA4 act at different stages of the cancer immunity cycle, with CTLA4 blockade at the earlier stage than PD-L1 blockage, the tumors treated with LipoDoxAtz and CTLA4 combination showed a significant reduction in growth compared to the combination with PD-L1. CD73 blockade had no effect in arresting tumor growth. Our data with combination of LipoDoxAtz + CTLA4 showed a significant tumor regression, increased survival and no toxicity to the overall health of mice. Moreover, mechanistic studies indicated upregulation of proteins promoting immunogenic cell death, namely HMGB1 and calreticulin with the combination group. Higher infiltration of CD8+ Tc cells and secretion of IFN-g confirmed the involvement of immunogenic factors to arrest tumor growth in highly aggressive 4T1 tumors. These findings indicate promising therapeutic potentials for our newly developed hypoxia-targeted DoxAtz in combination with antiCTLA4 for effective TNBC therapy in clinic.

Preoperative (Neoadjuvant) Chemotherapy

Preoperative (Neoadjuvant) Chemotherapy
Author: Joseph Ragaz
Publisher: Springer Science & Business Media
Total Pages: 172
Release: 2012-12-06
Genre: Medical
ISBN: 3642826717

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.

Cancer in Sub-Saharan Africa

Cancer in Sub-Saharan Africa
Author: Olufunso Adebola Adedeji
Publisher: Springer
Total Pages: 0
Release: 2018-06-12
Genre: Medical
ISBN: 9783319849348

This book discusses the current state of cancer pathway as it is relevant to sub-Saharan Africa and highlights differences in epidemiology and the underlying problems with management. It outlines the current practice and opinions in all forms of cancer, also highlighting future prospects. Starting by providing background information on the epidemiology and genomic variations, the book then goes on to look at Infection-related cancers and continues to prostate GI, breast cancer and ovarian and cervical cancer. The last part of the book focuses on delivery of affordable and accessible care. Palliative services and primary and transnational research, as well as clinical trials are also discussed. Written by a team of authors based in the UK, Nigeria, South Africa and the US. this book offers an overview of the current state and challenges of cancer care in sub-Saharan Africa, and it would be valuable to policy makers, researchers, funding organisations, and can be an adjunct to standard text books for students, residents and established doctors.

Novel Hormonal Combination Therapy for Triple Negative Breast Cancer

Novel Hormonal Combination Therapy for Triple Negative Breast Cancer
Author: Ankita Thakkar
Publisher:
Total Pages:
Release: 2016
Genre:
ISBN:

Anti-estrogen and anti-HER2 treatments have been among the first and most successful examples of targeted-therapy for breast cancers. However, around 10-20% of breast cancers lack estrogen receptor (ER) expression and HER2 amplification. Therefore, the treatment of ER-/HER2- Triple Negative Breast Cancer (TNBC) remains a major challenge due to lack of a druggable target. Currently, TNBCs are treated with non-targeted conventional chemotherapy and although they respond initially, less than 30% patients survive beyond 5 years highlighting the need for novel therapeutic strategies for this disease. We previously discovered that approximately two-thirds of TNBCs express Vitamin D Receptor (VDR) and/or Androgen Receptor (AR) and hypothesized that TNBCs that co-express both AR and VDR (HR2-av TNBC) could be treated by targeting both hormone receptors. To evaluate the feasibility of VDR/AR-targeted therapy in TNBC, we characterized 15 different breast cancer cell lines and identified two HR2-av TNBC lines. Surprisingly, we found that AR antagonist inhibited proliferation of most breast cancer cell lines in an AR-independent manner, raising questions regarding their mechanism of action. In contrast, combination treatment of the same cell lines with AR and VDR agonist hormones appeared to inhibit cell proliferation additively in a hormone receptor dependent manner. Moreover, cell viability was further decreased when AR/VDR agonist hormones were combined with chemotherapeutic drugs. The mechanisms of inhibition by AR/VDR agonist hormones included cell cycle arrest and apoptosis in TNBC cell lines. In addition, AR/VDR agonist hormones induced differentiation and inhibited cancer stem cells (CSCs) measured by reduction in tumorsphere formation efficiency, ALDH activity and CSC marker changes. Moreover, alternate AR and VDR ligands are available with enhanced or similar efficacy compared to the traditional agonists but with better side-effect profile. The combination of alternate AR and VDR ligands also showed additive decrease in cell viability in combination with each other as well as with chemotherapeutic agents in vitro. Thus, in summary, AR/VDR targeted agonist hormone therapy can inhibit HR2-av TNBC through multiple mechanisms in a receptor dependent manner and can be combined with chemotherapy.

Epithelial-Mesenchymal Plasticity in Cancer Metastasis

Epithelial-Mesenchymal Plasticity in Cancer Metastasis
Author: Mohit Kumar Jolly
Publisher: MDPI
Total Pages: 512
Release: 2020-12-29
Genre: Medical
ISBN: 3039367242

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.

Cancer Policy: Pharmaceutical Safety

Cancer Policy: Pharmaceutical Safety
Author: June M. McKoy
Publisher: Springer
Total Pages: 0
Release: 2019-01-16
Genre: Medical
ISBN: 9783319438948

Cancer Policy: Pharmaceutical Safety provides invaluable information on the interesting and compelling field of cancer drug safety. Identifying and understanding high-priority policy issues and key pharmacovigilance strategies is of paramount importance. In this volume, outstanding and original chapters provide an overview and synthesis of the latest thoughts and findings relating to drug safety in the cancer domain. Topics include natural language processing and pharmacovigilance of alternative cancer pharmaceuticals. The information presented in this volume will improve understanding of emerging strategies to identify adverse drug reactions and drug-drug interactions within the cancer setting and will highlight policies that have been instituted to improve cancer patient safety. In summary, Cancer Policy: Pharmaceutical Safety explores many of the important areas of pharmacovigilance research in oncology.

Drug Repurposing and Repositioning

Drug Repurposing and Repositioning
Author: Institute of Medicine
Publisher: National Academies Press
Total Pages: 95
Release: 2014-08-08
Genre: Medical
ISBN: 0309302072

Drug development can be time-consuming and expensive. Recent estimates suggest that, on average, it takes 10 years and at least $1 billion to bring a drug to market. Given the time and expense of developing drugs de novo, pharmaceutical companies have become increasingly interested in finding new uses for existing drugs - a process referred to as drug repurposing or repositioning. Historically, drug repurposing has been largely an unintentional, serendipitous process that took place when a drug was found to have an offtarget effect or a previously unrecognized on-target effect that could be used for identifying a new indication. Perhaps the most recognizable example of such a successful repositioning effort is sildenafil. Originally developed as an anti-hypertensive, sildenafil, marketed as Viagra and under other trade names, has been repurposed for the treatment of erectile dysfunction and pulmonary arterial hypertension. Viagra generated more than $2 billion worldwide in 2012 and has recently been studied for the treatment of heart failure. Given the widespread interest in drug repurposing, the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine hosted a workshop on June 24, 2013, in Washington, DC, to assess the current landscape of drug repurposing activities in industry, academia, and government. Stakeholders, including government officials, pharmaceutical company representatives, academic researchers, regulators, funders, and patients, were invited to present their perspectives and to participate in workshop discussions. Drug Repurposing and Repositioning is the summary of that workshop. This report examines enabling tools and technology for drug repurposing; evaluates the business models and economic incentives for pursuing a repurposing approach; and discusses how genomic and genetic research could be positioned to better enable a drug repurposing paradigm.