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Book Mechanisms of Therapeutic Resistance in Castration Resistant Prostate Cancer

Download or read book Mechanisms of Therapeutic Resistance in Castration Resistant Prostate Cancer written by Sarah Katherine Martin and published by . This book was released on 2015 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Therapy Resistance in Prostate Cancer

Download or read book Therapy Resistance in Prostate Cancer written by Hisham Bahmad and published by Elsevier. This book was released on 2023-10-24 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer (PCa) is among the most diagnosed cancers in men worldwide as well as one of the most common causes of cancer-related deaths. Despite the advances in treatment, the disease remains associated with poor survival and resistance to cytotoxic and targeted therapies. Therapy Resistance in Prostate Cancer: Mechanisms and Insights highlights the main mechanisms that are responsible for therapy resistance in PCa allowing researchers and clinicians to have a synopsis of current options and new therapies that can be proposed to overcome this resistance. Understanding the mechanisms responsible for chemotherapy resistance helps researchers all over the world to delve deeper into the pathways behind this resistance and potentially discover new therapeutic targets for PCa. Tackles the topic of resistance from a broader perspective, including, but not limited to, the role of the extracellular matrix and cancer stem cells in therapy resistance Creates understanding on how to develop novel therapies that specifically target CSCs to eliminate the regenerating capacity of the tumor and overcome therapy resistance Helps in identifying novel molecular biomarkers and potential therapeutic targets pertaining to the tumor microenvironment to overcome therapy resistance Provides a general view of the main pathways involved in PCa progression that will aid in understanding the mechanisms responsible for chemotherapy resistance

Book Nanostructures for Cancer Therapy

Download or read book Nanostructures for Cancer Therapy written by Alexandru Mihai Grumezescu and published by Elsevier. This book was released on 2017-04-11 with total page 922 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanostructures for Cancer Therapy discusses the available preclinical and clinical nanoparticle technology platforms and their impact on cancer therapy, including current trends and developments in the use of nanostructured materials in chemotherapy and chemotherapeutics. In particular, coverage is given to the applications of gold nanoparticles and quantum dots in cancer therapies. In addition to the multifunctional nanomaterials involved in the treatment of cancer, other topics covered include nanocomposites that can target tumoral cells and the release of antitumoral therapeutic agents. The book is an up-to-date overview that covers the inorganic and organic nanostructures involved in the diagnostics and treatment of cancer. Provides an examination of nanoparticle delivery systems for cancer treatment, illustrating how the use of nanotechnology can help provide more effective chemotherapeutic treatments Examines, in detail, the different types of nanomaterials used in cancer therapy, also explaining the effect of each Provides a cogent overview of recent developments in the use of nanostructured materials in chemotherapeutics, allowing readers to quickly familiarize themselves with this area

Book Response and Resistance in Castration Resistant Prostate Cancer

Download or read book Response and Resistance in Castration Resistant Prostate Cancer written by Hung-Ming Lam and published by Frontiers Media SA. This book was released on 2020-12-24 with total page 99 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Book Targeting Molecular Resistance in Castration Resistant Prostate Cancer

Download or read book Targeting Molecular Resistance in Castration Resistant Prostate Cancer written by Legnica Legnica Press and published by . This book was released on 2016-01-21 with total page 38 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple mechanisms of resistance contribute to the inevitable progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). Currently approved therapies for CRPC include systemic chemotherapy (docetaxel and cabazitaxel) and agents targeting the resistance pathways leading to CRPC, including enzalutamide and abiraterone. While there is significant survival benefit, primary and secondary resistance to these therapies develops rapidly. Up to one-third of patients have primary resistance to enzalutamide and abiraterone; the remaining patients eventually progress on treatment. Understanding the mechanisms of resistance resulting in progression as well as identifying new targetable pathways remains the focus of current prostate cancer research. We review current knowledge of mechanisms of resistance to the currently approved treatments, development of adjunctive therapies, and identification of new pathways being targeted for therapeutic purposes.

Book Molecular Mechanisms of Prostate Cancer Progression and Treatment Resistance

Download or read book Molecular Mechanisms of Prostate Cancer Progression and Treatment Resistance written by Yezi Zhu and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer is the most common type of cancer in American men and ranks second to lung cancer in cancer-related deaths. The growth and survival of primary prostate tumors requires physiological level of androgen. Thus hormone therapy has been used for treatment of primary prostate cancer. However, prostate cancer eventually progresses to a castration-resistant state. Understanding the molecular mechanisms leading to castration resistance is very critical for combat this lethal disease. The first part of this thesis will discuss the loss of Rho-GDP dissociation inhibitor [alpha] (RhoGDI[alpha]) as one of the molecular mechanisms leading to prostate cancer castration-resistant progression. My study demonstrated that RhoGDI[alpha] suppresses growth and survival of prostate cancer cells. In this part, I utilized the previously generated LNCaP-IL6+ cells which were able to grow in androgen-deprived condition. The protein expression profiles of LNCaP and LNCaP-IL6+ cells were compared using two-dimensional gel electrophoresis. Expression of RhoGDI[alpha] was reduced in LNCaP-IL6+ cells and was down-regulated in more aggressive prostate cancer cells compared to LNCaP cells. The effects of RhoGDI[alpha] in prostate cancer cells growth and survival were examined both in vitro and in vivo. Overexpression of RhoGDI[alpha] inhibited the growth and induced apoptosis of prostate cancer cells. RhoGDI[alpha] caused LNCaP-IL6+ cells reversal to androgen-sensitive state, and downregulation of RhoGDI[alpha] enhanced growth of androgen-sensitive LNCaP cells in androgen-deprived condition. In addition, RhoGDI[alpha] suppressed the tumorigenic ability and prostate-specific antigen (PSA) production of prostate tumor xenografts in vivo. The aberrant activation of androgen receptor (AR) is responsible for castration-resistant prostate cancer (CRPC) progression and regulation of AR-target genes such as PSA. My in vivo study showed RhoGDI[alpha] inhibited PSA production in the mice sera bearing tumors, indicating RhoGDI[alpha] inhibits AR signaling in prostate cancer cells. The effects of RhoGDI[alpha] on AR signaling will be further discussed. RhoGDI[alpha] was transiently or stably transfected into several prostate cancer cell lines including LNCaP, C4-2, CWR22Rv1 and DU145. The regulation of AR expression by RhoGDI[alpha] was analyzed by qRT-PCR and Western blot. Overexpression of RhoGDI[alpha] downregulated AR expression at both mRNA and protein levels. AR activity was measured by luciferase reporter assays and electrophoretic mobility shift analysis (EMSA). RhoGDI[alpha] was able to inhibit transactivation of AR target genes and prevent AR binding to androgen response element. Immunofluorescence assay was performed and overexpression of RhoGDI[alpha] prevented AR nuclear translocation induced by androgens. The interaction between RhoGDI[alpha] and AR was examined by co-immunoprecipitation assays. RhoGDI[alpha] was found to physically interact with the N-terminal domain of AR. Neuroendocrine differentiation (NED) is associated with castration-resistance of prostate cancer. It has been suggested as a marker of poor prognosis for prostate cancer. Paracrine interleukin-6 (IL-6) can mediate NED features in prostate cancer. The second part of this thesis will discuss the mechanism underlying IL-6-induced NED. RE1-silencing transcription factor (REST) is a main negative regulator of neurogenesis and represses expression of NED genes. I confirmed the IL-6-induced NED by cell morphological changes as well as the induction of NE markers such as neuron-specific enolase (NSE), chromogranin A (ChgA) and synaptophysin. The expression of REST was suppressed in IL-6-induced NED in LNCaP cells. To further study the impact of REST-mediated repression on NED in LNCaP cells, either wild-type REST or a dominant-positive form of REST, REST-VP16, in which both repressor domains of REST were replaced with the activation domain of the herpes simplex virus protein VP16, was introduced into LNCaP cells. Overexpression of exogenous wild type REST abrogated IL-6-induced NED in prostate cancer cells. Expression of the recombinant REST-VP16 fusion protein activated REST target genes and other neuronal differentiation genes and produced neuronal physiological properties. In addition, REST protein turnover was accelerated in IL-6 induced NE differentiated LNCaP cells via the ubiquitin-proteasome pathway, accompanied by a decrease in the expression of the deubiquitylase HAUSP, indicating that pathway(s) priming REST degradation may be involved in IL-6 induced NE differentiation. Docetaxel is the first-line standard treatment for CRPC. However, once tumors develop resistance to docetaxel, the treatment options are again limited. In the last part of this thesis, I will discuss the docetaxel resistance mechanisms and potential therapeutic strategies for docetaxel-resistant CRPC. I established a docetaxel resistant cell line, TaxR, by culturing C4-2B cells in docetaxel in a dose-escalation manner until cells were able to divide freely in 5 nM docetaxel. Global gene expression analysis by cDNA microarrays (approximately 28000 genes) was performed using mRNA from parental C4-2B and TaxR cells. ABCB1, which belongs to the ATP-binding cassette (ABC) transporter family, was identified among the top upregulated genes in TaxR cells. Overexpression of ABCB1 in TaxR cells has been validated by both real-time PCR and Western blot analysis. Downregulation of ABCB1 by specific shRNA or inhibiting ABCB1 activity by ABCB1 inhibitor elacridar restored docetaxel sensitivity in TaxR cells. Apigenin (4', 5, 7-trihydroxyflavone), a natural product belonging to the flavone family, downregulated ABCB1 protein expression in ubiquitin-proteasome pathway and overcame docetaxel resistance in TaxR cells. The effects of different anti-androgens like enzalutamide, abiraterone and bicalutamide on ABCB1 efflux activity were tested using rhodamine123 efflux assay. These antiandrogens inhibited ABCB1 efflux activity and reversed docetaxel resistance in TaxR cells in vitro. The reversal effect of bicalutamide was further confirmed in TaxR xenograft tumors, suggesting targeting ABCB1 could be a potential approach to resensitize docetaxel-resistant prostate cancer cells to docetaxel treatment.

Book Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance

Download or read book Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance written by Andrew Freywald and published by Academic Press. This book was released on 2020-11-17 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance, Volume 12, discusses new approaches that are being undertaken to counteract tumor plasticity, understand and tackle the interactions with the microenvironment, and disrupt the rewiring of malignant cells or bypass biological mechanism of resistance by using targeted radionuclide therapies. This book provides a unique opportunity to the reader to understand the fundamental causes of drug resistance and how different approaches are applied. It is a one-stop-shop to understand why it is so difficult to treat cancer, and why only a very few patients respond to therapy and a significant portion develop resistance. Despite a rapid development of more effective anti-cancer drugs and combination therapies, cancer remains the leading cause of lethality in the developed world. The main reason for this is the ability of heterogeneous subpopulations of tumor cells interacting with constantly evolving tumor microenvironment to resist elimination and eventually, trigger cancer relapse. In this book, experts review current concepts explaining molecular and biological mechanisms of cancer drug resistance and discussing advancing approaches for overcoming these therapeutic challenges. Provides the most updated knowledge on the mechanisms of cancer drug resistance and the emerging therapeutic approaches reviewed by experts in the field Brings detailed analyses of most important recently reported developments related to drug resistance and their relevance to overcoming it in cancer patients Discusses in-depth molecular mechanisms and novel concepts of cancer resistance to conventional and advanced therapies

Book Identification of Mechanisms of Resistance to Treatment with Abiraterone Acetate Or Enzalutamide in Patients with Castration   resistant Prostate Cancer  CRPC

Download or read book Identification of Mechanisms of Resistance to Treatment with Abiraterone Acetate Or Enzalutamide in Patients with Castration resistant Prostate Cancer CRPC written by and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book New Insights Into Prostate Cancer  New Biomarkers  Molecular Mechanisms  and Therapeutic Approaches

Download or read book New Insights Into Prostate Cancer New Biomarkers Molecular Mechanisms and Therapeutic Approaches written by Anna Perri and published by Frontiers Media SA. This book was released on 2024-08-05 with total page 133 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer is the second most common cancer in men, and prognosis varies with age, ethnicity, genetic background, and stage of progression. Disease progression that has been observed in a substantial proportion of patients despite androgen ablation, can arise from many factors, such as the presence of cells that are resistant de novo or acquire resistance induced by androgen-deprivation therapy (ADT) or androgen receptor antagonists.

Book De Novo Androgen Synthesis as a Mechanism Contributing to the Progression of Prostate Cancer to Castration Resistance

Download or read book De Novo Androgen Synthesis as a Mechanism Contributing to the Progression of Prostate Cancer to Castration Resistance written by and published by . This book was released on 2006 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer (CaP) is the leading cause of cancer in men affecting 24,700 Canadians each year and the third leading cause of cancer mortality with 4,300 deaths each year. CaP cells are derived from the prostate secretory epithelium and depend on androgen ligand activation of androgen receptor (AR) for survival, growth and proliferation. Androgen deprivation therapy (ADT) through pharmacological methods has been the leading form of CaP therapy since Huggin's discovery that castration induced the regression of CaP tumors in 1941. Unfortunately, the cancer often recurs within 2-4 years in what has classically been considered "androgen-independent" (AI) disease. Growing evidence implicates androgens and AR activation in this disease recurrence despite castration, suggesting that this terminology should be more appropriately called "castration-resistant" prostate cancer (CRPC). Firstly, AR is found amplified, overexpressed or mutated in a majority of recurrent cancers as compared to primary cancers and secondly, intratumoral testosterone levels remain the same pre- and post-ADT. Additionally, the measured intratumoral DHT levels are sufficient to activate AR in recurrent CaP cells despite low serum androgen levels suggesting that intratumoral androgens remain important mediators of AR-mediated CaP progression. Previously, we and others discovered that recurrent tumor cells have elevated levels of enzymes in the pathways necessary for androgen synthesis from cholesterol. The central hypothesis in this thesis is that after ADT, CaP cells adapt to synthesize their own androgens for survival and proliferation. The goal of this PhD dissertation is to decipher the mechanisms whereby prostate tumor cells de novo synthesize androgens and how these events contribute to recurrent CaP. We show herein that CRPC tumor cells are capable of producing androgens and that upstream cholesterol and fatty acids are key mediators in this process. Furthermore, CRPC tumor cells adapt quickly.

Book Allgemeines Lexikon der bildenden K  nstler

Download or read book Allgemeines Lexikon der bildenden K nstler written by and published by . This book was released on 1978 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Doxorubicin Resistance Mechanisms in Prostate Cancer

Download or read book Doxorubicin Resistance Mechanisms in Prostate Cancer written by Mallappa Sreevidya and published by . This book was released on 2023-10-16 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Doxorubicin is a widely used chemotherapy drug for the treatment of prostate cancer. However, drug resistance to doxorubicin has been a significant challenge in prostate cancer therapy. In this article, author Mallappa Sreevidya discusses the various mechanisms of doxorubicin resistance in prostate cancer. Drug resistance is a complex phenomenon involving multiple mechanisms, and understanding these mechanisms is crucial to overcoming resistance. Multidrug resistance (MDR) is one such mechanism, where cancer cells become resistant to multiple drugs. P-glycoprotein and ABC transporters are examples of efflux pumps that play a crucial role in MDR. The tumor microenvironment also plays a significant role in drug resistance by providing a protective niche for cancer cells. The progression of cancer and its ability to metastasize is another significant factor in drug resistance. Cancer stem cells, which are responsible for tumor initiation and growth, also play a role in drug resistance. Apoptosis and DNA damage are other mechanisms that contribute to doxorubicin resistance. Drug efflux, metabolism, and transport are additional mechanisms of doxorubicin resistance. Efflux pumps, such as P-glycoprotein, remove drugs from the cancer cells, reducing their effectiveness. Drug metabolism is another mechanism by which cancer cells become resistant to doxorubicin. Gene expression and epigenetic changes in cancer cells can also affect drug resistance by altering molecular pathways and cell signaling. Understanding the genetics and biology of prostate cancer is also essential for developing effective treatments. Cancer genetics and biology influence drug resistance and play a role in the development of new cancer therapies. Cancer immunology and personalized medicine are also promising areas of research for developing effective cancer treatments. Drug sensitivity and resistance can be evaluated through high-throughput screening and drug screening, which can lead to the development of new drugs or drug combinations to overcome resistance. Drug design and development are also essential for improving the efficacy of doxorubicin and other chemotherapy drugs. Clinical trials are necessary for evaluating the safety and efficacy of new cancer treatments. Biomarkers, such as predictive and prognostic biomarkers, can help identify patients who are likely to respond to treatment and monitor treatment response. In summary, understanding the mechanisms of doxorubicin resistance in prostate cancer is critical for developing effective cancer treatments. The complex interplay between cancer cells, the tumor microenvironment, and molecular pathways contributes to drug resistance. Developing new drugs and treatment strategies based on these mechanisms can improve the efficacy of doxorubicin and other chemotherapy drugs in the treatment of prostate cancer.

Book Therapeutic Resistance of Prostate Cancer Mediated by Cadherin T6

Download or read book Therapeutic Resistance of Prostate Cancer Mediated by Cadherin T6 written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In order to better understand the molecular basis for the development of therapeutic resistance by prostate cancer, we have undertaken experimentation in which we genetically compared therapy resistant prostate cancer cells to therapy sensitive prostate cancer cells. As a result of this comparison, we have identified a novel gene product, previously referred to as T6 (now referred to as Protocadherin-PC) that is highly upregulated when prostate cancer cells are selected for resistance to apoptotic agents in vitro and when these cells are selected for hormonal resistance in vivo. This progress report describes our success in characterizing the human Protocadherin-PC gene and gene product and in describing the probable mechanism through which this protein increases therapeutic resistance of prostate cancer cells. As a result of these studies, we believe that prostate cancer progresses to the state of therapeutic resistance in a mechanistically similar manner to that of human colon cancer and melanoma.

Book Evidence based Urology

    Book Details:
  • Author : Philipp Dahm
  • Publisher : John Wiley & Sons
  • Release : 2018-09-24
  • ISBN : 1119129885
  • Pages : 614 pages

Download or read book Evidence based Urology written by Philipp Dahm and published by John Wiley & Sons. This book was released on 2018-09-24 with total page 614 pages. Available in PDF, EPUB and Kindle. Book excerpt: An updated and revised resource to evidence-based urology information and a guide for clinical practice The revised and updated second edition of Evidence-Based Urology offers the most current information on the suitability of both medical and surgical treatment options for a broad spectrum of urological conditions based on the best evidence available. The text covers each of the main urologic areas in specific sections such as general urology, oncology, female urology, trauma/reconstruction, pediatric urology, etc. All the evidence presented is rated for quality using the respected GRADE framework. Throughout the text, the authors highlight the most patient-important, clinical questions likely to be encountered by urologists in day-to-day practice. A key title in the “Evidence-Based” series, this revised and expanded edition of Evidence-Based Urology contains new chapters on a variety of topics including: quality improvement, seminoma, nonseminomatous germ cell tumor, penile cancer, medical prophylaxis, vesicoureteral reflux disease, cryptorchidism, prenatal hydronephrosis, and myelodysplasia. This updated resource: Offers a guide that centers on 100% evidence approach to medical and surgical approaches Provides practical recommendations for the care of individual patients Includes nine new chapters on the most recently trending topics Contains information for effective patient management regimes that are supported by evidence Puts the focus on the most important patient and clinical questions that are commonly encountered in day-to-day practice Written for urologists of all levels of practice, Evidence-Based Urology offers an invaluable treasure-trove of evidence-based information that is distilled into guidance for clinical practice.

Book Human Cell Transformation

    Book Details:
  • Author : Johng S. Rhim
  • Publisher : Springer Science & Business Media
  • Release : 2011-09-15
  • ISBN : 1461402549
  • Pages : 239 pages

Download or read book Human Cell Transformation written by Johng S. Rhim and published by Springer Science & Business Media. This book was released on 2011-09-15 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rhim and Kremer’s state-of-the-art volume on Human Cell Transformation: Role of Stem Cells and the Microenvironment highlights the latest findings on the current state of human cell transformation model systems and provides the insight into the molecular and cellular changes involved in the conversion of normal cells to neoplastic cells. Chapters cover all recently developed novel human cell models. In addition, the rapidly growing fields of knowledge regarding not only stem cells in cancer progression, but also the role of the microenvironments in human carcinogenesis are discussed. A wealth of topics is presented including: · Derivation of epithelial, fibroblastic, and hematopoietic in vitro model systems · Oncogenes · Tumor suppressor genes · Viral transformation · In vitro model systems for viral, chemical and radiation carcinogenesis · Cell aging · The multistep nature of human carcinogenesis · The role of stem cells and the microenvironment in tumorigenesis · The genes involved in multistep carcinogenesis Unique in both scope and focus – devoted solely to human cell transformation systems – Human Cell Transformation: Role of Stem Cells and the Microenvironment provides unparalleled, in-depth coverage for cancer researchers, cell and molecular biologists, hematologists, virologists, and workers in related fields. Essential reading for everyone who needs to be kept up-to-date in this fast-paced area! Features ؠ Multistep models ؠ Breast cancer/Stem cells ؠ Prostate cancer/Stem cells ؠ Multistep / Genes

Book EIF4E Phosphorylation as a Mechanism of Resistance to MTOR and Androgen Receptor Inhibition in Advanced Prostate Cancer

Download or read book EIF4E Phosphorylation as a Mechanism of Resistance to MTOR and Androgen Receptor Inhibition in Advanced Prostate Cancer written by Leandro Salati D'Abronzo and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Treatment for prostate cancer patients who experience recurrent disease involves androgen deprivation therapy (ADT) as prostate tumors are primarily driven by activation of the androgen receptor (AR). However, most patients on this therapy relapse within a few years after which this treatment fails to extend survival and progresses to castration resistant prostate cancer (CRPC). Treatment for CRPC often involve inhibitors of the AR itself, however, patients on these treatments often fail as well. The main cause for the failure of many therapies is acquired resistance to treatment; therefore, there is an urgent need to better understand this resistance for improved disease management. Protein translation plays an important role in altering signaling pathways by modifying protein expression levels, and offer promising targets for preventing acquired resistance. mTOR (mechanistic target of rapamycin) is a key regulator of protein translation in humans, and multiple mTOR inhibitors have been developed over the years and used in many diseases as treatment, including prostate cancer. EIF4E is a key component of the translational mechanism in eukaryotic organisms and its phosphorylation has been implicated in resistance to several therapies in many cancer types. EIF4E is involved in both cap-dependent and –independent translation, however, mTOR regulates only cap-dependent translation. Here I demonstrate using my data from in vitro studies as well as human-derived tumor-xenograft models that phosphorylation of eIF4E at Ser209 plays a significant role in the resistance of prostate tumors to AR and mTOR inhibition, by changing the mechanism of protein translation from cap-dependent to cap-independent to maintain tumor cellular proliferation, growth and survival. In recent years, many clinical trials used combinations of mTOR and AR inhibitors in patients with CRPC who have failed first line therapy; many of these studies fail especially if they are conducted in patients who had been pre-treated with an AR inhibitor; whereas others partially succeed if they are used in untreated patients. The overall goal of my thesis is to study the role of eIF4E phosphorylation in the development of resistance to mTOR and AR inhibitors in prostate cancer. My data points to AR as a suppressor of eIF4E phosphorylation, therefore explaining why prior treatment with the AR inhibitor bicalutamide made patients resistant to a combination of bicalutamide with the mTOR inhibitor RAD001. Furthermore, our results show that the receptor tyrosine-protein kinase ErbB3 negatively regulates phosphorylation of eIF4E, and high levels of ErbB3 may be an indicative of tumors that would respond to the combination therapy. Taken together, our studies demonstrate the mechanisms by which prostate cancer acquires resistance to mTOR and AR inhibition and explain some of the responsible proteins and pathways that are involved in this process. We also indicate promising biomarkers for evaluation of therapy effectiveness with this combination in prostate cancer patients.

Book Epigenetic Biomarkers and Diagnostics

Download or read book Epigenetic Biomarkers and Diagnostics written by Jose Luis Garcia-Gimenez and published by Academic Press. This book was released on 2015-12-07 with total page 698 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epigenetic Biomarkers and Diagnostics comprises 31 chapters contributed by leading active researchers in basic and clinical epigenetics. The book begins with the basis of epigenetic mechanisms and descriptions of epigenetic biomarkers that can be used in clinical diagnostics and prognostics. It goes on to discuss classical methods and next generation sequencing-based technologies to discover and analyze epigenetic biomarkers. The book concludes with an account of DNA methylation, post-translational modifications and noncoding RNAs as the most promising biomarkers for cancer (i.e. breast, lung, colon, etc.), metabolic disorders (i.e. diabetes and obesity), autoimmune diseases, infertility, allergy, infectious diseases, and neurological disorders. The book describes the challenging aspects of research in epigenetics, and current findings regarding new epigenetic elements and modifiers, providing guidance for researchers interested in the most advanced technologies and tested biomarkers to be used in the clinical diagnosis or prognosis of disease. Focuses on recent progress in several areas of epigenetics, general concepts regarding epigenetics, and the future prospects of this discipline in clinical diagnostics and prognostics Describes the importance of the quality of samples and clinical associated data, and also the ethical issues for epigenetic diagnostics Discusses the advances in epigenomics technologies, including next-generation sequencing based tools and applications Expounds on the utility of epigenetic biomarkers for diagnosis and prognosis of several diseases, highlighting the study of these biomarkers in cancer, cardiovascular and metabolic diseases, infertility, and infectious diseases Includes a special section that discusses the relevance of biobanks in the maintenance of high quality biosamples and clinical-associated data, and the relevance of the ethical aspects in epigenetic studies