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FOXOs in Cancer Immunity: Knowns and Unknowns
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Youcai Deng, Fangjie Wang, Tiffany Hughes, Jianhua Yu In the tumor microenvironment (TME), cancer cells, stromal cells, and immune cells, along with their extracellular factors, have profound effects on either promoting or repressing anti-cancer immunity. Accumulating evidence has shown the paradoxical intrinsic role of the Forkhead box O (FOXO) family of transcription factors in cancer, which can act as a tumor repressor while also maintaining cancer stem cells. FOXOs also regulate cancer immunity. FOXOs promote antitumor activ...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

A transatlantic perspective on the integration of Immuno-Oncology Prognostic and Predictive Biomarkers in innovative clinical trial design
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): M. Morfouace, S.M. Hewitt, R. Salgado, K. Hartmann, S. Litiere, S. Tejpar, V. Golfinopoulos, T. Lively, M. Thurin, B. Conley, D. Lacombe Immuno-therapeutics aim to activate the body’s own immune system against cancer and are one of the most promising cancer treatment strategies, but currently limited by a variable response rate. Biomarkers may help to distinguish those patients most likely to respond to therapy; they may also help guide clinical decision making for combination therapies, dosing schedules, and determining p...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

FoxO transcription factors in cancer metabolism
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Raj Kumar Yadav, Anoop Singh Chauhan, Li Zhuang, Boyi Gan FoxO transcription factors serve as the central regulator of cellular homeostasis and are tumor suppressors in human cancers. Recent studies have revealed that, besides their classic functions in promoting cell death and inducing cell cycle arrest, FoxOs also regulate cancer metabolism, an emerging hallmark of cancer. In this review, we summarize the regulatory mechanisms employed to control FoxO activities in the context of cancer biology, and discuss FoxO function in me...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

Is Nanoclustering essential for all oncogenic KRas pathways? Can it explain why wild-type KRas can inhibit its oncogenic variant?
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang Membrane-anchored oncogenic KRas can dimerize, form nanoclusters, and signal through the MAPK (Raf/MEK/ERK) and PI3Kα/Akt/mTOR. Both pathways are needed in KRAS-driven proliferation. Here we ask: Is oncogenic KRas nanoclustering (or dimerization) essential for all KRas signaling pathways? Raf kinase domain dimerization, thus MAPK activation, requires KRas nanoclusters. By contrast, the PI3Kα heterodimer acts as a monomeric unit; thus, does PI3Kα activation and PI3K&a...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

Glycogen Synthase Kinases: Moonlighting Proteins with Theranostic Potential in Cancer
Publication date: Available online 5 January 2018 Source:Seminars in Cancer Biology Author(s): Siddavaram Nagini, Josephraj Sophia, Rajakishore Mishra Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase is an archetypal multifunctional moonlighting protein involved in diverse cellular processes including metabolism, insulin signaling, proliferation, differentiation, apoptosis, neuronal function and embryonic development. The two known isoforms, GSK-3α and GSK-3β that undergo activation/inactivation by post-translational, site-specific phosphorylation incorporate a vast number of substrates in their re...
Source: Seminars in Cancer Biology - January 5, 2018 Category: Cancer & Oncology Source Type: research

Bioblockades join the assault on small G protein signalling
Publication date: Available online 4 January 2018 Source:Seminars in Cancer Biology Author(s): Helen R. Mott, Darerca Owen Inhibition of Ras signalling has been a goal almost since its central role in cell signalling and its deregulation in disease were discovered. Early attempts at inhibiting its post-translational modification using peptidomimetics were successful in cell culture but failed spectacularly in clinical trials, making industry wary of targeting this critical oncoprotein. Small molecule inhibition of the protein-protein interactions involving Ras has also been difficult due to the nature of the interaction i...
Source: Seminars in Cancer Biology - January 4, 2018 Category: Cancer & Oncology Source Type: research

Targeting the Warburg effect for Cancer Treatment: Ketogenic Diets for Management of Glioma
Publication date: Available online 30 December 2017 Source:Seminars in Cancer Biology Author(s): Angela Poff, Andrew Kourtnik, Kathleen M. Egan, Solmaz Sahebjum, Dominic D’Agostino, Nagi B. Kumar (Source: Seminars in Cancer Biology)
Source: Seminars in Cancer Biology - December 30, 2017 Category: Cancer & Oncology Source Type: research

Network Science in Clinical Trials: A patient-centered approach
Publication date: Available online 24 December 2017 Source:Seminars in Cancer Biology Author(s): Venkata Manem, Roberto Salgado, Philippe Aftimos, Christos Sotiriou, Benjamin Haibe-Kains There has been a paradigm shift in translational oncology with the advent of novel molecular diagnostic tools in the clinic. However, several challenges are associated with the integration of these sophisticated tools into clinical oncology and daily practice. High-throughput profiling at the DNA, RNA and protein levels (omics) generate a massive amount of data. The analysis and interpretation of these is non-trivial but will allow a more...
Source: Seminars in Cancer Biology - December 24, 2017 Category: Cancer & Oncology Source Type: research

Enzyme targeting strategies for prevention and treatment of cancer: Implications for cancer therapy
Publication date: Available online 14 December 2017 Source:Seminars in Cancer Biology Author(s): Mohammad Hassan Baig, Mohd Adil, Rosina Khan, Surendar Dhadi, Khurshid Ahmad, Gulam Rabbani, Tufail Bashir, Mohammad Azhar Imran, Fohad Mabood Husain, Eun Ju Lee, Mohammad Amjad Kamal, Inho Choi Extensive growth of cancer in humans is a major cause of death. Numerous studies are being conducted to improve the early diagnosis, prevention, and treatment of cancer. Recent technological advancements in medical science and research indicate molecular target therapy holds much promise in cancer treatment. In the past, therapeutic an...
Source: Seminars in Cancer Biology - December 17, 2017 Category: Cancer & Oncology Source Type: research

Emerging biomarkers for immunomodulatory cancer treatment of upper gastrointestinal, pancreatic and hepatic cancers
Publication date: Available online 16 December 2017 Source:Seminars in Cancer Biology Author(s): Belinda Lee, Ryan Hutchinson, Hui-Li Wong, Jeanne Tie, Tracy Putoczki, Ben Tran, Peter Gibbs, Michael Christie Carcinomas of the oesophagus, stomach, pancreas and liver are common and account for a disproportionately high number of cancer deaths. There is a need for new treatment options for patients with advanced disease. Immunomodulatory treatments including immune checkpoint blockade offer a promising new approach, with efficacy shown in other solid tumour types. However, only a small proportion of patients with carcinomas ...
Source: Seminars in Cancer Biology - December 17, 2017 Category: Cancer & Oncology Source Type: research

Emerging biomarkers for the combination of radiotherapy and immune checkpoint blockers
Publication date: Available online 16 December 2017 Source:Seminars in Cancer Biology Author(s): Claire Lhuillier, Claire Vanpouille-Box, Lorenzo Galluzzi, Silvia Chiara Formenti, Sandra Demaria Over the past few years, multiple immune checkpoint blockers (ICBs) have achieved unprecedented clinical success and have been approved by regulatory agencies for the treatment of an increasing number of malignancies. However, only a limited fraction of patients responds to ICBs employed as a standalone intervention, calling for the development of combinatorial regimens. Radiation therapy (RT) stands out as a very promising candid...
Source: Seminars in Cancer Biology - December 17, 2017 Category: Cancer & Oncology Source Type: research

Understanding Preanalytical Variables and their Effects on Clinical Biomarkers of Oncology and Immunotherapy
Publication date: Available online 16 December 2017 Source:Seminars in Cancer Biology Author(s): Lokesh Agrawal, Kelly B. Engel, Sarah R. Greytak, Helen M. Moore Identifying a suitable course of immunotherapy treatment for a given patient as well as monitoring treatment response is heavily reliant on biomarkers detected and quantified in blood and tissue biospecimens. Suboptimal or variable biospecimen collection, processing, and storage practices have the potential to alter clinically relevant biomarkers, including those used in cancer immunotherapy. In the present review, we summarize effects reported for immunologicall...
Source: Seminars in Cancer Biology - December 17, 2017 Category: Cancer & Oncology Source Type: research

Enzyme targeting strategies and the prevention and treatment of cancer: implications for cancer therapy
Publication date: Available online 14 December 2017 Source:Seminars in Cancer Biology Author(s): Mohammad Hassan Baig, Mohd Adil, Rosina Khan, Surendar Dhadi, Khurshid Ahmad, Gulam Rabbani, Tufail Bashir, Mohammad Azhar Imran, Fohad Mabood Husain, Eun Ju Lee, Mohammad Amjad Kamal, Inho Choi Extensive growth of cancer in man is a major cause of death. Numerous studies are being conducted to improve the early diagnosis, prevention, and treatment of cancer, and recent technological advancements in medical science and research indicate molecular target therapy holds much promise. In the past, therapeutic and diagnostic target...
Source: Seminars in Cancer Biology - December 16, 2017 Category: Cancer & Oncology Source Type: research

Direct Inhibition of RAS: Quest for the Holy Grail?
Publication date: Available online 14 December 2017 Source:Seminars in Cancer Biology Author(s): Russell Spencer-Smith, John P. O’Bryan RAS GTPases (H-, K-, and N-RAS) are the most frequently mutated oncoprotein family in human cancer. However, the relatively smooth surface architecture of RAS and its picomolar affinity for nucleotide have given rise to the assumption that RAS is an “undruggable” target. Recent advancements in drug screening, molecular modeling, and a greater understanding of RAS function have led to a resurgence in efforts to pharmacologically target this challenging foe. This review fo...
Source: Seminars in Cancer Biology - December 16, 2017 Category: Cancer & Oncology Source Type: research

Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives
Publication date: Available online 15 December 2017 Source:Seminars in Cancer Biology Author(s): Hege Marie Vedeld, Ajay Goel, Guro E. Lind Each year, almost 4.1 million people are diagnosed with gastrointestinal (GI) cancers. Due to late detection of this disease, the mortality is high, causing approximately 3 million cancer-related deaths annually, worldwide. Although the incidence and survival differs according to organ site, earlier detection and improved prognostication have the potential to reduce overall mortality burden from these cancers. Epigenetic changes, including aberrant promoter DNA methylation, are common...
Source: Seminars in Cancer Biology - December 16, 2017 Category: Cancer & Oncology Source Type: research

Matrix Metalloproteinases: A challenging paradigm of cancer management
Publication date: Available online 16 November 2017 Source:Seminars in Cancer Biology Author(s): Ali Alaseem, Khalid Alhazzani, Priya Dondapati, Saad Alobid, Anupam Bishayee, Appu Rathinavelu Matrix metalloproteinases (MMPs) are members of zinc-dependent endopeptidases implicated in a variety of physiological and pathological processes. Over the decades, MMPs have been studied for their role in cancer progression, migration, and metastasis. As a result, accumulated evidence of MMPs incriminating role has made them an attractive therapeutic target. Early generations of broad-spectrum MMP inhibitors exhibited potent inhibit...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Mechanisms controlling the anti-neoplastic functions of FoxO proteins
Publication date: Available online 16 November 2017 Source:Seminars in Cancer Biology Author(s): Tianyun Hou, Zhiming Li, Ying Zhao, Wei-Guo Zhu The Forkhead box O (FoxO) proteins comprise a family of evolutionarily conserved transcription factors that predominantly function as tumor suppressors. These proteins assume diverse roles in the cellular anti-neoplastic response, including regulation of apoptosis and autophagy, cancer metabolism, cell-cycle arrest, oxidative stress and the DNA damage response. More recently, FoxO proteins have been implicated in cancer immunity and cancer stem-cell (CSC) homeostasis. Interesting...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

The role of paraoxonase in cancer
Publication date: Available online 21 November 2017 Source:Seminars in Cancer Biology Author(s): Tiziana Bacchetti, Gianna Ferretti, Amirhossein Sahebkar The paraoxonase (PON) gene family includes three proteins, PON1, PON2 and PON3. PON1 and PON3 are both associated with high-density lipoprotein (HDL) particles and exert anti-oxidant and anti-inflammatory properties. PON2 and PON3 are intracellular enzymes which modulate mitochondrial superoxide anion production and endoplasmic reticulum (ER) stress-induced apoptosis. The pleiotropic roles exerted by PONs have been mainly investigated in cardiovascular and neurodegenerat...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Challenges in Ras therapeutics in pancreatic cancer
Publication date: Available online 21 November 2017 Source:Seminars in Cancer Biology Author(s): Minsig Choi, Harold Bien, Adaobi Mofunanya, Scott Powers Pancreatic cancer is considered among the most aggressive and the least curable of all human malignancies. It is usually characterized by multiple aberrations in tumor suppressor genes and oncogenes, most notably activating mutations in KRAS. This review examines the various attempts that have been made to inhibit Kras and its downstream signaling pathways in pancreatic cancer with an emphasis on challenges related to clinical trials. Attempts include preventing the loca...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Re-evaluating the role of FOXOs in cancer
Publication date: Available online 21 November 2017 Source:Seminars in Cancer Biology Author(s): M. Hornsveld, T.B. Dansen, P.W. Derksen, B.M.T. Burgering FOXO transcription factors are negatively regulated by the PI3K-PKB/AKT signaling pathway and have been mainly considered to be tumor suppressors due to their inhibitory effect on cancer cell growth and survival. However, FOXOs can also support tumor development and progression by maintaining cellular homeostasis, facilitating metastasis and inducing therapy resistance. In agreement with these opposing views on the role of FOXOs in cancer, studies using FOXO levels or a...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Glioma epigenetics: From subclassification to novel treatment options
Publication date: Available online 21 November 2017 Source:Seminars in Cancer Biology Author(s): Olga Gusyatiner, Monika E. Hegi Gliomas are the most common malignant primary brain tumors, of which glioblastoma is the most malignant form (WHO grade IV), and notorious for treatment resistance. Over the last decade mutations in epigenetic regulator genes have been identified as key drivers of subtypes of gliomas with distinct clinical features. Most characteristic are mutations in IDH1 or IDH2 in lower grade gliomas, and histone 3 mutations in pediatric high grade gliomas that are also associated with characteristic DNA met...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Perspectives on the integration of Immuno-Oncology Biomarkers and drugs in a Health Care setting
Publication date: Available online 21 November 2017 Source:Seminars in Cancer Biology Author(s): K. Vermaelen, A. Waeytens, O. Kholmanskikh, M. Van den Bulcke, E. Van Valckenborgh Immunotherapies, specifically checkpoint inhibitors, are becoming an important component in cancer care with the most application now in melanoma and lung cancer patients. Some drawbacks that converge with this new evolution are the rather low response rates to these drugs and their high cost with a significant economic impact on the health care system. These major challenges can likely be circumvented by implementing a “personalized immun...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Food-derived 1,2-dicarbonyl compounds and their role in diseases
Publication date: Available online 22 November 2017 Source:Seminars in Cancer Biology Author(s): Michael Hellwig, Sabrina Gensberger-Reigl, Thomas Henle, Monika Pischetsrieder Reactive 1,2-dicarbonyl compounds (DCs) are generated from carbohydrates during food processing and storage and under physiological conditions. In the recent decades, much knowledge has been gained concerning the chemical formation pathways and the role of DCs in food and physiological systems. DCs are formed mainly by dehydration and redox reactions and have a strong impact on the palatability of food, because they participate in aroma and color fo...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Comprehensive pancancer genomic analysis reveals (RTK)-RAS-RAF-MEK as a key dysregulated pathway in cancer: Its clinical implications
Publication date: Available online 22 November 2017 Source:Seminars in Cancer Biology Author(s): Robin Imperial, Omer M Toor, Arif Hussain, Janakiraman Subramanian, Ashiq Masood Recent advances in Next Generation Sequencing (NGS) have provided remarkable insights into the genomic characteristics of human cancers that have spurred a revolution in the field of oncology. The mitogen-activated protein kinase pathway (MAPK) and its activating cell receptor, the receptor tyrosine kinases (RTKs), which together encompass the (RTK)-RAS-RAF-MEK-ERK axis, are central to oncogenesis. A pan-cancer genomics analysis presented in this ...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Role of bioactive lipofishins in prevention of inflammation and colon cancer
Publication date: Available online 24 November 2017 Source:Seminars in Cancer Biology Author(s): Valter R.M. Lombardi, Iván Carrera, Lola Corzo, Ramón Cacabelos Many clinical conditions exist in which it is desirable to stimulate or suppress the immune system, and many different drugs are able to do this. It is also well known that nutrition may affect human health and immune responses. Nutritional factors are crucial components of the diet and essential for normal growth and development of both vertebrate and invertebrate organisms. Many of these components have been shown to play different roles in the imm...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance
Publication date: Available online 24 November 2017 Source:Seminars in Cancer Biology Author(s): Shang Yao, Lavender Yuen-Nam Fan, Eric Wing-Fai Lam The FOXO3 and FOXM1 forkhead box transcription factors, functioning downstream of the essential PI3K-Akt, Ras-ERK and JNK/p38MAPK signalling cascades, are crucial for cell proliferation, differentiation, cell survival, senescence, DNA damage repair and cell cycle control. The development of resistance to both conventional and newly emerged molecularly targeted therapies is a major challenge confronting current cancer treatment in the clinic. Intriguingly, the mechanisms of re...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy
Publication date: Available online 26 November 2017 Source:Seminars in Cancer Biology Author(s): Lais Osmani, Frederic Askin, Edward Gabrielson, Qing Kay Li Recent large scale genomic studies from the Clinical Lung Cancer Genome Project have identified different driver gene mutations in the subtypes of non-small cell lung carcinoma (NSCLC). These findings not only lead to remarkable progress in targeted therapies for lung cancer patients, but also provide fundamental knowledge for the subclassification of NSCLC. More recently, the advancement and clinical application of immunotherapy have reinforced the need for the accur...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

PD-L1, inflammation, non-coding RNAs, and neuroblastoma: Immuno-oncology perspective
Publication date: Available online 28 November 2017 Source:Seminars in Cancer Biology Author(s): Palanisamy Nallasamy, Srinivas Chava, Sumit S. Verma, Shruti Mishra, Santhi Gorantla, Don W. Coulter, Siddappa N. Byrareddy, Surinder K. Batra, Subash C. Gupta, Kishore B. Challagundla Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells ...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Special Issue: Mitochondria in Cancer
Publication date: December 2017 Source:Seminars in Cancer Biology, Volume 47 Author(s): Keshav K Singh, Josephine S. Modica-Napolitano (Source: Seminars in Cancer Biology)
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

MicroRNA regulation of K-Ras in pancreatic cancer and opportunities for therapeutic intervention
Publication date: Available online 2 December 2017 Source:Seminars in Cancer Biology Author(s): Saswati Karmakar, Garima Kaushik, Ramakrishna Nimmakayala, Satyanarayana Rachagani, Moorthy P. Ponnusamy, Surinder K. Batra The Ras family of GTPases is involved in cell proliferation, cell survival, and angiogenesis. It is upregulated in several cancers, including pancreatic cancer (PC) and leads to uncontrolled growth and aggressiveness. PC is well known to be a lethal disease with poor prognosis, plagued by limited therapeutic modalities. MicroRNAs (miRNAs), which are short non-coding RNA molecules, have recently emerged as ...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting
Publication date: Available online 2 December 2017 Source:Seminars in Cancer Biology Author(s): James V. Michael, Lawrence E. Goldfinger For decades oncogenic RAS proteins were considered undruggable due to a lack of accessible binding pockets on the protein surfaces. Seminal early research in RAS biology uncovered the basic paradigm of post-translational isoprenylation of RAS polypeptides, typically with covalent attachment of a farnesyl group, leading to isoprenyl-mediated RAS anchorage at the plasma membrane and signal initiation at those sites. However, the failure of farnesyltransferase inhibitors to translate to the...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Immuno-oncology from the perspective of somatic evolution
Publication date: Available online 6 December 2017 Source:Seminars in Cancer Biology Author(s): Santiago González, Nadezda Volkova, Philip Beer, Moritz Gerstung The past years have witnessed significant success for cancer immunotherapies that activate a patient’s immune system against their cancer cells. At the same time our understanding of the genetic changes driving tumor evolution have progressed dramatically. The study of cancer genomes has shown that tumors are best understood as cell populations governed by the rules of evolution, leading to the emergence and spread of cell lineages with pathogenic mut...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics
Publication date: Available online 8 December 2017 Source:Seminars in Cancer Biology Author(s): Priti S. Hegde, Jeffrey J. Wallin, Christoph Mancao The critical role of angiogenesis in promoting tumor growth and metastasis has been well established scientifically, and consequently blocking this pathway as a therapeutic strategy has demonstrated great clinical success for the treatment of cancer. The holy grail however, has been the identification of patients who derive significant survival benefit from this class of agents. Here we attempt to delineate the diverse mechanisms related to anti-VEGF including its role as an a...
Source: Seminars in Cancer Biology - December 14, 2017 Category: Cancer & Oncology Source Type: research

PAX3-FOXO1: Zooming in on an “undruggable” target
Publication date: Available online 14 November 2017 Source:Seminars in Cancer Biology Author(s): Marco Wachtel, Beat W. Schäfer Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promisi...
Source: Seminars in Cancer Biology - November 14, 2017 Category: Cancer & Oncology Source Type: research

Dna-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia
Publication date: Available online 9 November 2017 Source:Seminars in Cancer Biology Author(s): Christian Flotho, Sebastian Sommer, Michael Lübbert Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiv...
Source: Seminars in Cancer Biology - November 10, 2017 Category: Cancer & Oncology Source Type: research

Enzymes involved in tumor-driven angiogenesis: a valuable target for anticancer therapy
Publication date: Available online 8 November 2017 Source:Seminars in Cancer Biology Author(s): Biagio Ricciuti, Jennifer Foglietta, Vanessa Bianconi, Amirhossein Sahebkar, Matteo Pirro Angiogenesis plays a pivotal role in cancer progression and is required for tissue invasion and metastasis. Starting with Folkman’s initial observations in 1971, basic research continued to shed new molecular insight into this multifaceted process, leading to the development of several anti-angiogenic drugs. To date, anti-vascular endothelial growth factor monoclonal antibodies, such as bevacizumab and ramucirumab, and receptor tyros...
Source: Seminars in Cancer Biology - November 9, 2017 Category: Cancer & Oncology Source Type: research

Molecular and enzoinformatics perspectives of targeting Polo-like kinase 1 in cancer therapy
Publication date: Available online 6 November 2017 Source:Seminars in Cancer Biology Author(s): Shazi Shakil, Mohammad H. Baig, Shams Tabrez, Syed M. Danish Rizvi, Syed K. Zaidi, Ghulam M. Ashraf, Shakeel A. Ansari, Aftab Aslam Parwaz Khan, Mohammad H. Al-Qahtani, Adel M. Abuzenadah, Adeel G. Chaudhary Cancer is a disease that has been the focus of scientific research and discovery and continues to remain so. Polo-like kinases (PLKs) are basically serine/threonine kinase enzymes that control cell cycle from yeast to humans. PLK-1 stands for ‘Polo-like kinase-1’. It is the most investigated protein among PLKs. ...
Source: Seminars in Cancer Biology - November 7, 2017 Category: Cancer & Oncology Source Type: research

Breast cancer genomics and immuno-oncological markers to guide immune therapies
Publication date: Available online 2 November 2017 Source:Seminars in Cancer Biology Author(s): D. Hammerl, M. Smid, A.M. Timmermans, S. Sleijfer, J.W.M. Martens, R. Debets There is an increasing awareness of the importance of tumor – immune cell interactions to the evolution and therapy responses of breast cancer (BC). Not surprisingly, numerous studies are currently assessing the clinical value of immune modulation for BC patients. However, till now durable clinical responses are only rarely observed. It is important to realize that BC is a heterogeneous disease comprising several histological and molecular subtyp...
Source: Seminars in Cancer Biology - November 6, 2017 Category: Cancer & Oncology Source Type: research

Do all roads lead to the Rome? The glycation perspective!
Publication date: Available online 4 November 2017 Source:Seminars in Cancer Biology Author(s): Saheem Ahmad, Firoz Akhter, Uzma Shahab, Zeeshan Rafi, Mohd. Sajid Khan, Rabia Nabi, Mohd Salman Khan, Khurshid Ahmad, Jalaluddin Mohammad Ashraf, Moinuddin Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (...
Source: Seminars in Cancer Biology - November 5, 2017 Category: Cancer & Oncology Source Type: research

Vitamin C – a new player in regulation of the cancer epigenome
Publication date: Available online 1 November 2017 Source:Seminars in Cancer Biology Author(s): Linn Gillberg, Andreas D. Ørskov, Minmin Liu, Laurine B.S. Harsløf, Peter A. Jones, Kirsten Grønbæk Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their cent...
Source: Seminars in Cancer Biology - November 3, 2017 Category: Cancer & Oncology Source Type: research

Current insights into functions of phospholipase A2 receptor in normal and cancer cells: More questions than answers
Publication date: Available online 2 November 2017 Source:Seminars in Cancer Biology Author(s): Olga Sukocheva, Mario Menschikowski, Albert Hagelgans, Nagendra Sastry Yarla, Gabriele Siegert, Pallu Reddanna, Anupam Bishayee Lipid signaling network was proposed as a potential target for cancer prevention and treatment. Several recent studies revealed that phospholipid metabolising enzyme, phospholipase A2 (PLA2), is a critical regulator of cancer accelerating pathologies and apoptosis in several types of cancers. In addition to functioning as an enzyme, PLA2 can activate a phospholipase A2 receptor (PLA2R1) in plasma membr...
Source: Seminars in Cancer Biology - November 3, 2017 Category: Cancer & Oncology Source Type: research

Implications of farnesyltransferase and its inhibitors as a promising strategy for cancer therapy
Publication date: Available online 31 October 2017 Source:Seminars in Cancer Biology Author(s): Sergey G. Klochkov, Margarita E. Neganova, Nagendra Sastry Yarla, Madhukiran Parvathaneni, Bechan Sharma, Vadim V. Tarasov, George Barreto, Sergey O. Bachurin, Ghulam Md Ashraf, Gjumrakch Aliev Ras proteins have been reported to play key role in oncologic diseases. Ras proteins are associated with cellular membranes for its carcinogenic activities through post-translational modifications, including farnesylation. Farnesyltransferase is responsible for a type of Ras membrane targeting, which leads to cancer origin and progressio...
Source: Seminars in Cancer Biology - October 31, 2017 Category: Cancer & Oncology Source Type: research

The role of dietary pattern, foods, nutrients and nutraceuticals in supporting cancer prevention and treatment
Publication date: October 2017 Source:Seminars in Cancer Biology, Volume 46 (Source: Seminars in Cancer Biology)
Source: Seminars in Cancer Biology - October 30, 2017 Category: Cancer & Oncology Source Type: research

Oxidation, glycation and glycoxidation —The vicious cycle and lung cancer
Publication date: Available online 19 October 2017 Source:Seminars in Cancer Biology Author(s): Saheem Ahmad, Mohd Yasir Khan, Zeeshan Rafi, Hamda Khan, Zeba Siddiqui, Shahnawaz Rehman, Uzma Shahab, Mohd Sajid Khan, Mohd Saeed, Sultan Alouffi, Mohd Shahnawaz Khan The combine effect of oxidative and glycative stress predisposed to glycoxidation, and their outcomes that play critical role in lung cancer have been examined in different ways. The therapeutic approaches for lung cancer are still unsatisfactory. We observe some unclear and decisive pathways which might play an important role in targeting lung cancer. The roadma...
Source: Seminars in Cancer Biology - October 30, 2017 Category: Cancer & Oncology Source Type: research

Epigenetics of Malignant Melanoma
Publication date: Available online 23 October 2017 Source:Seminars in Cancer Biology Author(s): Bruce Moran, Romina Silva, Antoinette S. Perry, William M. Gallagher Patients with malignant melanoma generally have a good prognosis if the disease presents prior to metastasis. Due to progress with targeted and immunotherapies, the median survival of metastatic melanoma patients is now over 2 years. The disease is characterised by one of the highest somatic mutation rates observed amongst cancer types, with a specific mutational signature based on UV radiation damage evident. Highly prevalent mutations, such as the BRAFV600E ...
Source: Seminars in Cancer Biology - October 30, 2017 Category: Cancer & Oncology Source Type: research

Ousting RAGE in melanoma: A viable therapeutic target?
Publication date: Available online 24 October 2017 Source:Seminars in Cancer Biology Author(s): Deeba N. Syed, Ahmed Aljohani, Durdana Waseem, Hasan Mukhtar Melanoma remains an important health concern, given the steady increase in incidence and acquisition of resistance to systemic therapies. The receptor for advanced glycation end products (RAGE) initially identified for its binding to advanced glycation end products was subsequently acknowledged as a pattern recognition receptor given its ability to recognize similar structural elements within numerous ligands. Recent studies have elucidated a plausible role of RAGE in...
Source: Seminars in Cancer Biology - October 30, 2017 Category: Cancer & Oncology Source Type: research

KRAS, YAP, and obesity in pancreatic cancer: a signaling network with multiple loops
Publication date: Available online 24 October 2017 Source:Seminars in Cancer Biology Author(s): Guido Eibl, Enrique Rozengurt Pancreatic ductal adenocarcinoma (PDAC) continues to be a lethal disease with no efficacious treatment modalities. The incidence of PDAC is expected to increase, at least partially because of the obesity epidemic. Increased efforts to prevent or intercept this disease are clearly needed. Mutations in KRAS are initiating events in pancreatic carcinogenesis supported by genetically engineered mouse models of the disease. However, oncogenic KRAS is not entirely sufficient for the development of fully ...
Source: Seminars in Cancer Biology - October 30, 2017 Category: Cancer & Oncology Source Type: research

Genito-urinary genomics and emerging biomarkers for immunomodulatory cancer treatment
Publication date: Available online 12 October 2017 Source:Seminars in Cancer Biology Author(s): Thomas Gevaert, Rodolfo Montironi, Antonio Lopez-Beltran, Arno Van Leenders, Yves Allory, Dirk De Ridder, Frank Claessens, Mark Kockx, Murat Akand, Steven Joniau, George Netto, Louis Libbrecht Immunotherapy is gradually becoming a key factor in the therapeutic algorithm for patients with genito-urinary (GU) cancers at different stages of disease. Robust and reliable biomarkers are crucial for an appropriate inclusion of patients in clinical trials and for a reliable patient selection for treatments with immunomodulatory drugs. ...
Source: Seminars in Cancer Biology - October 12, 2017 Category: Cancer & Oncology Source Type: research

Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: a report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer
Publication date: Available online 9 October 2017 Source:Seminars in Cancer Biology Author(s): Maria Vittoria Dieci, Nina Radosevic-Robin, Susan Fineberg, Gert van den Eynden, Nils Ternes, Frederique Penault-Llorca, Giancarlo Pruneri, Timothy M. D’Alfonso, Sandra Demaria, Carlos Castaneda, Joselyn Sanchez, Sunil Badve, Stefan Michiels, Veerle Bossuyt, Federico Rojo, Baljit Singh, Torsten Nielsen, Giuseppe Viale, Seong-Rim Kim, Stephen Hewitt, Stephan Wienert, Sybille Loibl, David Rimm, Fraser Symmans, Carsten Denkert, Sylvia Adams, Sherene Loi, Roberto Salgado Morphological evaluation of tumor-infiltrating lymphocyt...
Source: Seminars in Cancer Biology - October 9, 2017 Category: Cancer & Oncology Source Type: research

Emerging targets in cancer immunotherapy
Publication date: Available online 5 October 2017 Source:Seminars in Cancer Biology Author(s): Samantha Burugu, Amanda R. Dancsok, Torsten O. Nielsen The first generation of immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1) targeted natural immune homeostasis pathways, co-opted by cancers, to drive anti-tumor immune responses. These agents led to unprecedented results in patients with previously incurable metastatic disease and may become first-line therapies for some advanced cancers. However, these agents are efficacious in only a minority of patients. Newer strategies are becoming available that target add...
Source: Seminars in Cancer Biology - October 8, 2017 Category: Cancer & Oncology Source Type: research