Download or read book Treatment induced Breast Cancer Dormancy and Relapse written by Rebecca Caroline Keim and published by . This book was released on 2014 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: When breast tumor cells encounter stress due to cancer therapies, they may enter a dormant state, escaping from treatment-induced apoptosis. Dormant cells may eventually regain proliferative capabilities and cause recurrent metastatic disease, which is the leading cause of mortality in breast cancer patients. We sought to determine if a high dose of radiation therapy (RT) or combined chemo-immunotherapy, with and without the blockade of autophagy by chloroquine (CQ), could overcome treatment-induced tumor dormancy or relapse. We found that autophagy contributes in part to treatment-induced tumor dormancy. We also found that three therapeutic strategies were successful in inhibiting or preventing tumor relapse. These include: 18Gy/day RT, chemotherapy combined with the blockade of autophagy, and combined chemo-immunotherapy. Follow-up studies are needed to determine the feasibility of preventing tumor relapse by prolonging tumor dormancy versus eliminating dormant tumor cells.

Download or read book Preconditioning of the Tumor Microenvironment by Means of Low Dose Chemotherapies for an Effective Immunotherapy of Breast Cancer written by Hussein F. Aqbi and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer mortality is mainly due to distant recurrence of the disease arising from dormant tumor cells established by cancer therapies. Patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy. We explored two strategies: 1) transient blockade of autophagy with chloroquine (CQ), which blocks fusion of autophagosomes and lysosomes during ADR treatment, and 2) permanent inhibition of autophagy by a stable knockdown of ATG5 (ATG5KD), which inhibits the formation of autophagosomes in MMC during and after ADR treatment. We found that while CQ prolonged tumor dormancy, but that stable knockdown of autophagy resulted in early escape from dormancy and recurrence. Interestingly, ATG5KD MMC contained an increased frequency of ADR-induced polyploid-like cells and rendered MMC resistant to immunotherapy. On the other hand, a transient blockade of autophagy did not affect the sensitivity of MMC to immunotherapy. Our observations suggest that while chemotherapy-induced autophagy may facilitate tumor relapse, cell-intrinsic autophagy delays tumor relapse, in part, by inhibiting the formation of polyploid-like tumor dormancy. Although immunotherapy of breast cancer by means of anti-HER2 antibodies prolongs survival of breast cancer patients, disease recurrence remains a major challenge. On the other hand administration of human vaccines against infectious disease in a preventive setting or during latency/dormancy has been successful in offering a cure. Here, we sought to use adoptive immunotherapy (AIT) at the time of tumor dormancy in order to prevent progression of breast cancer. We used a low dose immunogenic chemotherapy by means of 5-FU, Adriamycin, and Cyclophosphamide (FAC) in order to stabilize tumor progression prior to AIT using autologous tumor-reactive lymphocytes. Low dose FAC established local tumor dormancy, inhibited distant tumor dormancy occurring long before distant metastasis, and induced predominate a Ki67- quiescent type of tumor dormancy, which is less susceptible to tumor immunoediting. Dormant tumor cells expressed the cell survival pathways, including the endothelin receptor/ligand (ETRA, ETRB and ET-1) and PD-L1, thereby protecting them from elimination by AIT. In addition, tumor-reactive CD8+ T cells also produced ET-1 as a survival ligand for ETRA positive tumor cells. A combination of AIT with the blockade of tumor cell survival pathways resulted in a significant improvement of AIT against tumor dormancy. We also showed that the inhibition Bcl-xL downstream of the tumor cell survival pathways is specifically effective against dormant tumor cells, suggesting a combination of AIT with small molecules inhibitors of Bcl-xL. Altogether, we showed that distant tumor dormancy is established long before distant recurrence of breast cancer, and that the expression of several tumor cell survival pathways in dormant cells protects them from immunotherapy. Our results suggest that immunotherapeutic targeting of tumor dormancy combined with the blockade of a common downstream cell survival pathway could prevent tumor progression and recurrence of the disease.

Download or read book The Contribution of the ETS domain Transcription Factor EHF to Breast Cancer Dormancy and Recurrence written by Lauren M. Pferdehirt and published by . This book was released on 2015 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is the most common cause of cancer-related death and is the most frequently diagnosed cancer in women worldwide. Mortality from breast cancer is principally due to tumor recurrence, which may be diagnosed up to 20 years after treatment of the primary tumor. Since relapse is a consequence of the persistence of residual tumor cells, identifying the mechanisms involved in tumor cell survival and escape from therapy is essential for the development of more effective strategies for improving patient outcomes. Using a genetically-engineered mouse model for breast cancer dormancy and recurrence, we now report that inhibition of HER2/neu signaling in primary tumors induces cellular senescence and that this process may serve as a barrier to tumor relapse. We find that the ETS-domain transcription factor Ehf is up-regulated following acute HER2/neu signaling inhibition and induces senescence in mouse mammary tumor cells. Notably, Ehf expression is lost in residual breast cancer cells that survive tumor regression, as well as in recurrent tumors. Analogous to its behavior in response to targeted down-regulation of the HER2/neu pathway, EHF is acutely up-regulated in human breast cancer cells following Adriamycin treatment, but down-regulated in tumor cells that survive neoadjuvant chemotherapy in breast cancer patients. Consistent with a model in which EHF down-regulation promotes tumor cell survival following therapy, low EHF expression in primary breast cancers is associated with a poor response to neoadjuvant chemotherapy and an increased risk of relapse in women with breast cancer. Collectively, our findings demonstrate that senescence is a conserved response to HER2/neu signaling inhibition in oncogene-addicted breast cancer cells and identify EHF as a potential regulator of HER2/neu inactivation-induced senescence and tumor cell survival following targeted therapy and chemotherapy.

Download or read book Modeling Breast Cancer Dormancy and Recurrence Following Oncogenic Pathway Inhibition written by Jason R. Ruth and published by . This book was released on 2014 with total page 366 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer recurrence is the primary cause of mortality in breast cancer, and although advances have been made in the treatment of primary breast cancer, recurrent breast cancer remains uncurable. Targeted therapy has had a major impact on survival across multiple cancer types, including breast cancer, however patients who respond to targeted therapy ultimately relapse. Residual disease, the tumor cells that survive initial therapy, represent an attractive therapeutic target, however little is known about the biology of these cells. We use mouse models of breast cancer to investigate the phenotype of residual disease that survives targeted therapy, and to explore approaches to inhibit tumor recurrence. Residual disease exhibits cellular dormancy in models driven by distinct oncogenic pathways. Gene expression profiling reveals that residual tumor cells are enriched for a phenotype associated with normal and neoplastic stem-like cells, but are not enriched for tumor initiative cells. Interventions that inhibit inflammatory signaling inhibit tumor recurrence, however increasing inflammation promotes tumor recurrence. Inflammatory macrophages may be leukocytes that promote inflammation and drive recurrence in these models. Together, our findings present a more comprehensive picture of residual tumor cells surviving targeted therapy, and suggest possible therapeutic strategies for targeting residual disease that gives rise to cancer recurrence.

Download or read book Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer written by Michail Ignatiadis and published by Springer Science & Business Media. This book was released on 2012-04-23 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: This important book provides up-to-date information on a series of topical issues relating to the approach to minimal residual disease in breast cancer patients. It first explains how the study of minimal residual disease and circulating and disseminated tumor cells (CTCs/DTCs) can assist in the understanding of breast cancer metastasis. A series of chapters then discuss the various technologies available for the detection and characterization of CTCs and DTCs, pinpointing their merits and limitations. Detailed consideration is given to the relevance of CTCs and DTCs, and their detection, to clinical research and practice. The role of other blood-based biomarkers is also addressed, and the closing chapters debate the challenges facing drug and biomarker co-development and the use of CTCs for companion diagnostic development. This book will be of interest and assistance to all who are engaged in the modern management of breast cancer.

Download or read book Perioperative Inflammation as Triggering Origin of Metastasis Development written by Michael W. Retsky and published by Springer. This book was released on 2018-08-12 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book will explain previously unconnected clinical data such as why mammography works better for women age 50-59 than it does for women age 40-49, why adjuvant chemotherapy works best for premenopausal patients with positive lymph nodes, and it may also explain the racial disparity in outcome. In particular, it points to the perioperative period when systemic inflammation persists for a week or so. This can lead to a variety of mechanisms whereby single cancer cells (perhaps from the marrow) begin division and angiogenesis of dormant avascular micrometastases occurs leading to early relapses. With chapters presented from distinguished scientists and physicians in a variety of specialties that relate to and border the effects we present, this volume can be used as a reference for practicing physicians and as a jumping-off point for researchers to explore new therapeutic opportunities.

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.

Download or read book Tumor intrinsic Inflammatory Pathways Associated with Tumor Dormancy and Recurrence written by Savannah E. Butler and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The successful treatment of breast cancer is limited due to a fraction of tumor cells escaping drug-treatment by entering a dormant state, only to relapse years or decades later at distant sites. Host-driven chronic inflammatory cells such as M2 macrophages play an important role in tumorigenesis, but the role of tumor-intrinsic inflammatory signaling involved in tumor dormancy and recurrence is unknown. We sought to determine the role of tumor-intrinsic inflammatory pathways in mouse mammary carcinoma cells (MMC) treated with Adriamycin (ADR), a clinically relevant chemotherapeutic drug. We found that ADR-induced dormant tumor cells autonomously produced pro-inflammatory cytokines, in vitro. MMC treated with Chloroquine (CQ) prior to ADR treatment displayed a delay in relapse, or prolonging of dormancy, when compared to ADR-treated MMC. Additional gene array data showed predicated activation of NF-[kappa]B p65 in ADR-treated dormant MMC that eventually relapsed. These data suggest that the anti-inflammatory function of CQ led to prolonged dormancy. To test this, we investigated the role of inflammatory signaling pathways directly by shRNA-mediated knockdown and CRISPR-Cas9-mediated knockout of NF-[kappa]B p65 in MMC. We found that knockdown of NF-[kappa]B p65 resulted in fewer dormant cells after ADR treatment and reduced rate of relapse, in vitro. NF-[kappa]B p65 was also found to reduce the immunomodulatory effects of ADR, with shNF-[kappa]B p65 showing increased upregulation of neu upon ADR treatment. Additionally, we found NF-[kappa]B p65 to be associated with a higher infiltration of CD8+ T cells and anti-tumor T cell responses. Our findings suggest a dual role of tumor-intrinsic NF-[kappa]B p65 pathway, allowing for escape from drug treatment through dormancy which leads to relapse, but also for proper lymphocyte infiltration and subsequent anti-tumor activity.

Download or read book Cellular Immune Mechanisms and Tumor Dormancy written by T. H. M. Stewart and published by CRC Press. This book was released on 2017-07-28 with total page 387 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular Immune Mechanisms and Tumor Dormancy features the work of internationally recognized experts from various disciplines as they discuss the phenomenon of tumor dormancy in humans. Animal models are described in which cellular and molecular components of the immune control of dormancy have been identified, and the relevance of these models to human cancer patients is recognized. Data derived from studies of organ transplantation, adjuvant chemotherapy, radiotherapy, anaesthesia, surgery, and whole blood transfusion is presented to show the vulnerability of cellular mechanisms maintaining dormancy. The potential for increasing the incidence of dormancy in micro metastases is also shown for non-small cell lung cancer, lymphoma, and leukemia. Cellular Immune Mechanisms and Tumor Dormancy is an important reference volume that will benefit researchers from many disciplines, including immunologists, pathologists, surgeons, and clinicians

Download or read book Pulmonary Metastasis written by Leonard Weiss and published by Macmillan Reference USA. This book was released on 1978 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Autophagy and Senescence in Cancer Therapy written by and published by Academic Press. This book was released on 2021-04-13 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Cancer Research, Volume 150, the latest release in this ongoing series, covers the relationship(s) between autophagy and senescence, how they are defined, and the influence of these cellular responses on tumor dormancy and disease recurrence. Specific sections in this new release include Autophagy and senescence, converging roles in pathophysiology, Cellular senescence and tumor promotion: role of the unfolded protein response, autophagy and senescence in cancer stem cells, Targeting the stress support network regulated by autophagy and senescence for cancer treatment, Autophagy and PTEN in DNA damage-induced senescence, mTOR as a senescence manipulation target: A forked road, and more. Addresses the relationship between autophagy and senescence in cancer therapy Covers autophagy and senescence in tumor dormancy Explores autophagy and senescence in disease recurrence

Download or read book Adjuvant Therapy for Breast Cancer written by Monica Castiglione and published by Springer Science & Business Media. This book was released on 2009-07-11 with total page 483 pages. Available in PDF, EPUB and Kindle. Book excerpt: Adjuvant treatment is administered prior to or as follow up to surgical procedures for breast cancer. Proven success in using medical therapies allowing for breast conserving procedures or reducing risk of occurrence. Although there has been much progress towards a cure, including the introduction of new targeted therapies, metastasizing cancer remains highly incurable.

Download or read book Endocrine Therapy in Breast Cancer written by William R. Miller and published by CRC Press. This book was released on 2002-03-08 with total page 395 pages. Available in PDF, EPUB and Kindle. Book excerpt: This reference evaluates and describes the latest strategies for hormone suppression and blockade in the management of early and advanced stage breast cancer and explores the effects of tamoxifen, selective estrogen receptor modulators (SERMs), aromatase inhibitors, and their combination on both breast cancers and normal tissues. Endocrine T

Download or read book Prevention of Bone Metastases written by Markus Joerger and published by Springer Science & Business Media. This book was released on 2012-01-05 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: Bone metastases continue to be a major cause of morbidity in cancer patients, but improved understanding of the biology of bone metastases has led to the identification of drugs that are of potential value in not only their treatment but also their prevention. This book, written by recognized experts in the field, provides a detailed overview of current knowledge on this subject. One important focus of the book is the efficacy of bisphosphonates in preventing bone metastases in patients with breast, lung, and prostate cancer and disease progression in cases of multiple myeloma. The combined use of bisphosphonates and cytostatics is also discussed, with a report on first clinical data. Further topics addressed include the significance of the bone microenvironment, special issues in the elderly patient, the use of bone turnover markers, and initial findings obtained with denosumab.

Download or read book Surgical Papers written by William Halsted and published by . This book was released on 1984 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: 2000, Gift of Dr. Marion C. Anderson.

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.

Download or read book Tumor Dormancy and Recurrence written by Yuzhuo Wang and published by Humana Press. This book was released on 2017-08-31 with total page 85 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume will be the first to provide a comprehensive description of tumor dormancy. It will define the clinical and biological aspects of this phenomenon, as well as the cellular and molecular mechanisms associated with tumor dormancy. Chapters will be authored by world-renewed experts who are conducting cutting-edge research in the field. A unique feature will be a conclusive paragraph detailing future development and foreseeable clinical applications at the end of each chapter. The volume will serve as a fundamental instrument for every researcher and clinician interested in the field of tumor dormancy as well as a means of disseminating stimulating concepts and prompting the development of innovative technological solutions.