Cell Stress, Metabolic Reprogramming, and Cancer

Download Cell Stress, Metabolic Reprogramming, and Cancer PDF Online Free

Author :
Publisher : Frontiers Media SA
ISBN 13 : 2889455653
Total Pages : 68 pages
Book Rating : 4.8/5 (894 download)

DOWNLOAD NOW!


Book Synopsis Cell Stress, Metabolic Reprogramming, and Cancer by : Sergio Giannattasio

Download or read book Cell Stress, Metabolic Reprogramming, and Cancer written by Sergio Giannattasio and published by Frontiers Media SA. This book was released on 2018-08-31 with total page 68 pages. Available in PDF, EPUB and Kindle. Book excerpt: The present eBook presents one review, five mini-reviews, and an opinion article on the achievements and perspectives of studies on important aspects of cancer cell metabolic reprogramming whose mechanisms and regulation are still largely elusive. It also sheds light on certain novel functional components, which rewires cell metabolism in tumor transformation.

Cell Stress, Metabolic Reprogramming, and Cancer

Download Cell Stress, Metabolic Reprogramming, and Cancer PDF Online Free

Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (136 download)

DOWNLOAD NOW!


Book Synopsis Cell Stress, Metabolic Reprogramming, and Cancer by :

Download or read book Cell Stress, Metabolic Reprogramming, and Cancer written by and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The present eBook presents one review, five mini-reviews, and an opinion article on the achievements and perspectives of studies on important aspects of cancer cell metabolic reprogramming whose mechanisms and regulation are still largely elusive. It also sheds light on certain novel functional components, which rewires cell metabolism in tumor transformation.

The Heterogeneity of Cancer Metabolism

Download The Heterogeneity of Cancer Metabolism PDF Online Free

Author :
Publisher : Springer
ISBN 13 : 331977736X
Total Pages : 186 pages
Book Rating : 4.3/5 (197 download)

DOWNLOAD NOW!


Book Synopsis The Heterogeneity of Cancer Metabolism by : Anne Le

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

Metabolism in Cancer

Download Metabolism in Cancer PDF Online Free

Author :
Publisher : Springer
ISBN 13 : 3319421182
Total Pages : 272 pages
Book Rating : 4.3/5 (194 download)

DOWNLOAD NOW!


Book Synopsis Metabolism in Cancer by : Thorsten Cramer

Download or read book Metabolism in Cancer written by Thorsten Cramer and published by Springer. This book was released on 2016-08-24 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.

Redox and Metabolic Circuits in Cancer

Download Redox and Metabolic Circuits in Cancer PDF Online Free

Author :
Publisher : Frontiers Media SA
ISBN 13 : 2889456358
Total Pages : 183 pages
Book Rating : 4.8/5 (894 download)

DOWNLOAD NOW!


Book Synopsis Redox and Metabolic Circuits in Cancer by : Salvatore Rizza

Download or read book Redox and Metabolic Circuits in Cancer written by Salvatore Rizza and published by Frontiers Media SA. This book was released on 2018-12-21 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: Living cells require a constant supply of energy for the orchestration of a variety of biological processes in fluctuating environmental conditions. In heterotrophic organisms, energy mainly derives from the oxidation of carbohydrates and lipids, whose chemical bonds breakdown allows electrons to generate ATP and to provide reducing equivalents needed to restore the antioxidant systems and prevent from damage induced by reactive oxygen and nitric oxide (NO)-derived species (ROS and RNS). Studies of the last two decades have highlighted that cancer cells reprogram the metabolic circuitries in order to sustain their high growth rate, invade other tissues, and escape death. Therefore, this broad metabolic reorganization is mandatory for neoplastic growth, allowing the generation of adequate amounts of ATP and metabolites, as well as the optimization of redox homeostasis in the changeable environmental conditions of the tumor mass. Among these, ROS, as well as NO and RNS, which are produced at high extent in the tumor microenvironment or intracellularly, have been demonstrated acting as positive modulators of cell growth and frequently associated with malignant phenotype. Metabolic changes are also emerging as primary drivers of neoplastic onset and growth, and alterations of mitochondrial metabolism and homeostasis are emerging as pivotal in driving tumorigenesis. Targeting the metabolic rewiring, as well as affecting the balance between production and scavenging of ROS and NO-derived species, which underpin cancer growth, opens the possibility of finding selective and effective anti-neoplastic approaches, and new compounds affecting metabolic and/or redox adaptation of cancer cells are emerging as promising chemotherapeutic tools. In this Research Topic we have elaborated on all these aspects and provided our contribution to this increasingly growing field of research with new results, opinions and general overviews about the extraordinary plasticity of cancer cells to change metabolism and redox homeostasis in order to overcome the adverse conditions and sustain their “individualistic” behavior under a teleonomic viewpoint.

Cancer as a Metabolic Disease

Download Cancer as a Metabolic Disease PDF Online Free

Author :
Publisher : John Wiley & Sons
ISBN 13 : 1118310306
Total Pages : 482 pages
Book Rating : 4.1/5 (183 download)

DOWNLOAD NOW!


Book Synopsis Cancer as a Metabolic Disease by : Thomas Seyfried

Download or read book Cancer as a Metabolic Disease written by Thomas Seyfried and published by John Wiley & Sons. This book was released on 2012-05-18 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.

Metabolism of Cancer Cells and Immune Cells in the Tumor Microenvironment

Download Metabolism of Cancer Cells and Immune Cells in the Tumor Microenvironment PDF Online Free

Author :
Publisher : Frontiers Media SA
ISBN 13 : 2889457850
Total Pages : 87 pages
Book Rating : 4.8/5 (894 download)

DOWNLOAD NOW!


Book Synopsis Metabolism of Cancer Cells and Immune Cells in the Tumor Microenvironment by : Yongsheng Li

Download or read book Metabolism of Cancer Cells and Immune Cells in the Tumor Microenvironment written by Yongsheng Li and published by Frontiers Media SA. This book was released on 2019-03-20 with total page 87 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metabolism of glucose, lipids, amino acids, and nucleotides represents the fundamental capability of host to utilize distinct nutrients and energy to support diverse function of different cell lineages. Cancer cells undergo the Warburg Effect to adapt to the microenvironment composed by stromal cells and immune cells. The crosstalk among cancer cells and immune cells orchestrate tumor progression. In the tumor microenvironment, immune cells also show metabolic reprogramming. For example, naive or memory T cells switch from the oxidation of fatty acids to glycolysis and glutaminolysis after activation; meanwhile massive glucose and glutamine are transported into cells to meet their metabolic demands. Defective glucose or glutamine metabolism impairs the differentiation and expansion of helper T cells. The molecular pathways that control immune cell metabolism and function are intimately linked. Understanding such metabolic reprogramming of immune cells in the tumor microenvironment could offer new directions in manipulation of peripheral immune responses. Recent findings in immune cell metabolism hold the promising possibilities by metabolic manipulation of immune cells towards clinical therapeutics for treating cancer. This Research Topic includes updated findings and views in the metabolism of cancer cells and immune cells in the tumor microenvironment.

Tumor Cell Metabolism

Download Tumor Cell Metabolism PDF Online Free

Author :
Publisher : Springer
ISBN 13 : 3709118247
Total Pages : 373 pages
Book Rating : 4.7/5 (91 download)

DOWNLOAD NOW!


Book Synopsis Tumor Cell Metabolism by : Sybille Mazurek

Download or read book Tumor Cell Metabolism written by Sybille Mazurek and published by Springer. This book was released on 2015-01-19 with total page 373 pages. Available in PDF, EPUB and Kindle. Book excerpt: The four sections of this book cover cell and molecular biology of tumor metabolism, metabolites, tumor microenvironment, diagnostics and epigenetics. Written by international experts, it provides a thorough insight into and understanding of tumor cell metabolism and its role in tumor biology. The book is intended for scientists in cancer cell and molecular biology, scientists in drug and diagnostic development, as well as for clinicians and oncologists.

Cancer Metabolism: Molecular Targeting and Implications for Therapy

Download Cancer Metabolism: Molecular Targeting and Implications for Therapy PDF Online Free

Author :
Publisher : Frontiers Media SA
ISBN 13 : 2889453227
Total Pages : 116 pages
Book Rating : 4.8/5 (894 download)

DOWNLOAD NOW!


Book Synopsis Cancer Metabolism: Molecular Targeting and Implications for Therapy by : Shanmugasundaram Ganapathy-Kanniappan

Download or read book Cancer Metabolism: Molecular Targeting and Implications for Therapy written by Shanmugasundaram Ganapathy-Kanniappan and published by Frontiers Media SA. This book was released on 2017-11-03 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: Development of an effective anticancer therapeutic necessitates the selection of cancer-related or cancer-specific pathways or molecules that are sensitive to intervention. Several such critical yet sensitive molecular targets have been recognized, and their specific antagonists or inhibitors validated as potential therapeutics in preclinical models. Yet, majority of anticancer principles or therapeutics show limited success in the clinical translation. Thus, the need for the development of an effective therapeutic strategy persists.

“Altered energy metabolism” in cancer is one of the earliest known biochemical phenotypes which dates back to the early 20th century. The German scientist, Otto Warburg and his team (Warburg, Wind, Negelein 1926; Warburg, Wind, Negelein 1927) provided the first evidence that the glucose metabolism of cancer cells diverge from normal cells. This phenomenal discovery on deregulated glucose metabolism or cellular bioenergetics is frequently witnessed in majority of solid malignancies. Currently, the altered glucose metabolism is used in the clinical diagnosis of cancer through positron emission tomography (PET) imaging. Thus, the “deregulated bioenergetics” is a clinically relevant metabolic signature of cancer cells, hence recognized as one of the hallmarks of cancer (Hanahan and Weinberg 2011). Accumulating data unequivocally demonstrate that, besides cellular bioenergetics, cancer metabolism facilitates several cancer-related processes including metastasis, therapeutic resistance and so on. Recent reports also demonstrate the oncogenic regulation of glucose metabolism (e.g. glycolysis) indicating a functional link between neoplastic growth and cancer metabolism. Thus, cancer metabolism, which is already exploited in cancer diagnosis, remains an attractive target for therapeutic intervention as well. The Frontiers in Oncology Research Topic “Cancer Metabolism: Molecular Targeting and Implications for Therapy” emphases on recent advances in our understanding of metabolic reprogramming in cancer, and the recognition of key molecules for therapeutic targeting. Besides, the topic also deliberates the implications of metabolic targeting beyond the energy metabolism of cancer. The research topic integrates a series of reviews, mini-reviews and original research articles to share current perspectives on cancer metabolism, and to stimulate an open forum to discuss potential challenges and future directions of research necessary to develop effective anticancer strategies. Acknowledgment I sincerely thank the Frontiers for providing the opportunity and constant support throughout the process of this research topic and eBook production. I gratefully acknowledge all the authors for their valuable contributions. Finally, I would like to thank my brother, Saravana Kumar, G.K., whose personal sacrifices and unflinching encouragement made my career in science possible. References: Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell. 144(5):646-74. Warburg O, Wind F, Negelein E. 1926. Über den stoffwechsel der tumoren in körper. Klinische Wochenschrift. 5:829-32. Warburg O, Wind F, Negelein E. 1927. The metabolism of tumors in the body. J Gen Physiol. 8(6):519-30.

Cancer Cell Metabolism: A Potential Target for Cancer Therapy

Download Cancer Cell Metabolism: A Potential Target for Cancer Therapy PDF Online Free

Author :
Publisher : Springer Nature
ISBN 13 : 9811519919
Total Pages : 191 pages
Book Rating : 4.8/5 (115 download)

DOWNLOAD NOW!


Book Synopsis Cancer Cell Metabolism: A Potential Target for Cancer Therapy by : Dhruv Kumar

Download or read book Cancer Cell Metabolism: A Potential Target for Cancer Therapy written by Dhruv Kumar and published by Springer Nature. This book was released on 2020-02-13 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book illustrates various aspects of cancer cell metabolism, including metabolic regulation in solid tumours vs. non-solid tumours, the molecular pathways involved in its metabolism, and the role of the tumour microenvironment in the regulation of cancer cell metabolism. It summarizes the complexity of cancer cell metabolism in terms of the switch from anaerobic to aerobic glycolysis and how mitochondrial damage promotes aerobic glycolysis in cancer cells. The respective chapters provide the latest information on the metabolic remodelling of cancer cells and elucidate the important role of the signalling pathways in reprogramming of cancer cell metabolism. In addition, the book highlights the role of autophagy in cancer cell metabolism, and how metabolic crosstalk between cancer cells and cancer-associated fibroblasts promotes cancer cell progression. In closing, it summarizes recent advancements in drug development through targeting cancer metabolism.

Mitochondria and Cancer

Download Mitochondria and Cancer PDF Online Free

Author :
Publisher : Springer Science & Business Media
ISBN 13 : 0387848355
Total Pages : 294 pages
Book Rating : 4.3/5 (878 download)

DOWNLOAD NOW!


Book Synopsis Mitochondria and Cancer by : Keshav Singh

Download or read book Mitochondria and Cancer written by Keshav Singh and published by Springer Science & Business Media. This book was released on 2009-04-05 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nearly a century of scientific research has revealed that mitochondrial dysfunction is one of the most common and consistent phenotypes of cancer cells. A number of notable differences in the mitochondria of normal and cancer cells have been described. These include differences in mitochondrial metabolic activity, molecular composition of mitochondria and mtDNA sequence, as well as in alteration of nuclear genes encoding mitochondrial proteins. This book, Mitochondria and Cancer, edited by Keshav K. Singh and Leslie C. Costello, presents thorough analyses of mitochondrial dysfunction as one of the hallmarks of cancer, discusses the clinical implications of mitochondrial defects in cancer, and as unique cellular targets for novel and selective anti-cancer therapy.

The Tumour Microenvironment

Download The Tumour Microenvironment PDF Online Free

Author :
Publisher : John Wiley & Sons
ISBN 13 : 9780471499596
Total Pages : 322 pages
Book Rating : 4.4/5 (995 download)

DOWNLOAD NOW!


Book Synopsis The Tumour Microenvironment by : Jamie A. Goode

Download or read book The Tumour Microenvironment written by Jamie A. Goode and published by John Wiley & Sons. This book was released on 2001-11-28 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ergebnisse von in vitro-Studien lassen vermuten, dass sich der pH-Wert in einem Tumor auf die Wirksamkeit von Chemo- oder Strahlentherapien auswirken kann. Wie aber sieht die Beziehung zwischen der Tumorentwicklung und dem pH-Wert aus? Können ein niedriger pH-Wert oder ein Sauerstoffmangel die Carcinogenese hemmen? Wo bieten sich therapeutische Ansätze? Anwort auf diese und andere Fragen finden Sie in diesem Band. In interdisziplinärer Weise wurden Beiträge aus der Grundlagenforschung und der klinischen Praxis zusammengetragen.

Carbohydrate-based Inducers of Cellular Stress for Targeting Cancer Cell Metabolism

Download Carbohydrate-based Inducers of Cellular Stress for Targeting Cancer Cell Metabolism PDF Online Free

Author :
Publisher :
ISBN 13 :
Total Pages : 200 pages
Book Rating : 4.:/5 (122 download)

DOWNLOAD NOW!


Book Synopsis Carbohydrate-based Inducers of Cellular Stress for Targeting Cancer Cell Metabolism by : Fidelis Toloyi Ndombera

Download or read book Carbohydrate-based Inducers of Cellular Stress for Targeting Cancer Cell Metabolism written by Fidelis Toloyi Ndombera and published by . This book was released on 2018 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: ABSTRACT CARBOHYDRATE-BASED INDUCERS OF CELLULAR STRESS FOR TARGETING CANCER CELL METABOLISM by FIDELIS TOLOYI NDOMBERA May 2018 Advisor: Dr. Young-Hoon Ahn Major: Chemistry (Biochemistry) Degree: Doctor of Philosophy Metabolic reprogramming and redox control of cancer cells is vital for their proliferation, but also provides selective strategies for treating cancer. Increased generation of reactive oxygen species (ROS) and an intricate control of redox status in cancer cells relative to normal cells provide a basis for designing ROS-inducing anticancer agents. In my work, I designed, synthesized and evaluated carbohydrate-based small molecules for ROS-generation, cytotoxicity and redox signaling and stress response. Our data from assays, including cell viability assays, enzyme inhibition studies, Western blot studies, click chemistry, and metabolomics, reveal that our compound (K8A) is more potent than 2-DG, a well-known carbohydrate-derived inhibitor of glycolysis. We reported discovery of carbohydrate-based small molecules with the property of blocking altered metabolic activity and enhancing ROS with potential therapeutic benefits for targeting cancer cells. Importantly, we investigated the mechanism of action of our potent compound that involve disruption of protein glycosylation in cancer with downstream effects on cancer metabolism.

Metabolic Adaptation to Cell Growth and Proliferation in Normal and Pathological Conditions

Download Metabolic Adaptation to Cell Growth and Proliferation in Normal and Pathological Conditions PDF Online Free

Author :
Publisher : Frontiers Media SA
ISBN 13 : 2889454843
Total Pages : 70 pages
Book Rating : 4.8/5 (894 download)

DOWNLOAD NOW!


Book Synopsis Metabolic Adaptation to Cell Growth and Proliferation in Normal and Pathological Conditions by : Lluis Fajas

Download or read book Metabolic Adaptation to Cell Growth and Proliferation in Normal and Pathological Conditions written by Lluis Fajas and published by Frontiers Media SA. This book was released on 2018-04-27 with total page 70 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proliferating cells must adapt their metabolism to fulfill the increased requirements for energy demands and biosynthetic intermediates. This adaptation is particularly relevant in cancer, where sustained rapid proliferation combined with the harsh conditions of the tumor microenvironment represent a major metabolic challenge. Noteworthy, metabolic reprogramming is now considered one of the hallmarks of cancer. However, the one size fits all rarely applies to the metabolic rewiring occurring in cancer cells, which ultimately depends on the combination of several factors such as the tumor’s origin, the specific genetic alterations and the surrounding microenvironment. In the present Research Topic, we compile a series of articles that discuss different metabolic adaptations that proliferating cells undergo to sustain growth and division, as well as the potential therapeutic window to treat certain pathologies, with a special focus on cancer.

Metabolic Regulation under Oxidative Stress in Cancer

Download Metabolic Regulation under Oxidative Stress in Cancer PDF Online Free

Author :
Publisher : Frontiers Media SA
ISBN 13 : 2832535690
Total Pages : 165 pages
Book Rating : 4.8/5 (325 download)

DOWNLOAD NOW!


Book Synopsis Metabolic Regulation under Oxidative Stress in Cancer by : Ali Vaziri-Gohar

Download or read book Metabolic Regulation under Oxidative Stress in Cancer written by Ali Vaziri-Gohar and published by Frontiers Media SA. This book was released on 2023-10-10 with total page 165 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Autophagy and Metabolism

Download Autophagy and Metabolism PDF Online Free

Author :
Publisher : Elsevier
ISBN 13 : 032399945X
Total Pages : 364 pages
Book Rating : 4.3/5 (239 download)

DOWNLOAD NOW!


Book Synopsis Autophagy and Metabolism by : Dhruv Kumar

Download or read book Autophagy and Metabolism written by Dhruv Kumar and published by Elsevier. This book was released on 2022-08-06 with total page 364 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy and Metabolism: Potential Target for Cancer Therapy presents updates on autophagy in cancer metabolism and how it can be used to develop new, more efficient treatments. Written by experts in the field, the book presents recent research and explains how to translate it to the clinical setting. Sections discuss tumor cell metabolism and autophagy as therapeutic targets, autophagy regulation in cancer, signaling pathways in metabolic dysregulation in solid tumors, metabolic stress and cell death pathways, and the role of the tumor microenvironment. In addition, topics cover combined targeting autophagy, metabolism for cancer therapy, and the autophagy effect on immune cell metabolism. This will be a valuable resource for researchers, oncologists, graduate students, and members of the biomedical field who are interested in learning more about the interaction between autophagy and cancer metabolism. Presents valuable and updated information on the mechanisms of autophagy in cancer metabolism Discusses the various metabolic pathways linked with autophagy that can be a major target for chemotherapeutic strategies Explains how autophagy supports tumor growth by activating metabolic phenotypes in cancer cells and the therapeutic interventions available to halt the process

Age-associated Metabolic Reprogramming, Oxidative Stress Response, and Cancer Progression

Download Age-associated Metabolic Reprogramming, Oxidative Stress Response, and Cancer Progression PDF Online Free

Author :
Publisher :
ISBN 13 :
Total Pages : 139 pages
Book Rating : 4.:/5 (11 download)

DOWNLOAD NOW!


Book Synopsis Age-associated Metabolic Reprogramming, Oxidative Stress Response, and Cancer Progression by : Jyung Mean Son

Download or read book Age-associated Metabolic Reprogramming, Oxidative Stress Response, and Cancer Progression written by Jyung Mean Son and published by . This book was released on 2017 with total page 139 pages. Available in PDF, EPUB and Kindle. Book excerpt: Considering PDAC being an age-related disease and a dismal 5-y survival of less than 9%, this study investigates whether stromal aging regulates PDAC progression. Results show that NHFs from older healthy individuals stimulate proliferation of PDAC cells compared to younger NHFs. Results from an in vivo study show that rate of tumor growth in xenografts of PDAC cells cultured with the old NHFs is significantly increased compared to the co-cultures of the young NHFs. In addition, decreased survival was also observed in mice carrying xenograft of co-culture of PDAC and the old NHFs compared to the young NHFs. Results from quantitative RT-PCR assays show that arachidonic acid lipoxygenase (ALOX12) expression decreased in PDAC, but increased in stromal fibroblasts in an age-dependent manner. Molecular inhibition of ALOX12 in the old NHFs suppressed PDAC proliferation in co-culture. These results show that aging of stromal fibroblasts aging promotes progression of PDAC, and identified ALOX12 and its metabolite 12-hydroxyeicosatetraenoic acid (12(S)-HETE) as critical regulators of PDAC proliferation. Taken together, findings from this project demonstrate that age-associated metabolic reprogramming of NHFs from glycolysis in young to mitochondrial respiration in old regulates fibroblasts-induced stimulation of proliferation of human PDAC. Importantly, results from this study are anticipated to contribute to the development of novel approaches targeting stromal aging for cancer prevention and therapy response.