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Seminars in Cancer Biology

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https://www.readbyqxmd.com/read/29146205/pax3-foxo1-zooming-in-on-an-undruggable-target
#1
REVIEW
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 promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets...
November 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#2
REVIEW
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 responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29128510/enzymes-involved-in-tumor-driven-angiogenesis-a-valuable-target-for-anticancer-therapy
#3
REVIEW
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 tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, regorafenib and axitinib) have had a profound impact on the way we treat patients with advanced cancer, providing in some cases unprecedented clinical benefit...
November 8, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29122685/molecular-and-enzoinformatics-perspectives-of-targeting-polo-like-kinase-1-in-cancer-therapy
#4
REVIEW
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. It is crucial for intracellular processes, hence a 'hot' anticancer drug-target. Accelerating innovations in Enzoinformatics and associated molecular visualization tools have made it possible to literally perform a 'molecular level walk' traversing through and observing the minutest contours of the active site of relevant enzymes...
November 6, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29113952/do-all-roads-lead-to-the-rome-the-glycation-perspective
#5
REVIEW
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 (HIF-1α), β-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules...
November 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29104026/current-insights-into-functions-of-phospholipase-a2-receptor-in-normal-and-cancer-cells-more-questions-than-answers
#6
REVIEW
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 membrane. While the list of PLA2 targets extends to glucose homeostasis, intracellular energy balance, adipocyte development, and hepatic lipogenesis, the PLA2R1 downstream effectors are few and scarcely investigated...
November 2, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29104025/breast-cancer-genomics-and-immuno-oncological-markers-to-guide-immune-therapies
#7
REVIEW
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 subtypes, which cannot be expected to be equally immunogenic and therefore not equally sensitive to single immune therapies...
November 2, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29102482/vitamin-c-a-new-player-in-regulation-of-the-cancer-epigenome
#8
REVIEW
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 central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care...
November 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29100957/implications-of-farnesyltransferase-and-its-inhibitors-as-a-promising-strategy-for-cancer-therapy
#9
REVIEW
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 progression. Inhibitors of farnesyltransferase have been developed as novel anticancer agents for several cancers. In this review, role of farnesyltransferase in cancer progression and development has been discussed...
October 31, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29079306/ousting-rage-in-melanoma-a-viable-therapeutic-target
#10
REVIEW
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 melanoma progression through modulation of inflammatory, proliferative and invasive cellular responses...
October 24, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29079305/kras-yap-and-obesity-in-pancreatic-cancer-a-signaling-network-with-multiple-loops
#11
REVIEW
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 invasive PDAC...
October 24, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29074395/epigenetics-of-malignant-melanoma
#12
REVIEW
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 BRAF(V600E), in the MAPK cascade indicate truncal involvement of this pathway in the earliest stage of melanoma...
October 23, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29055529/oxidation-glycation-and-glycoxidation-the-vicious-cycle-and-lung-cancer
#13
REVIEW
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 roadmap of signaling pathway includes p38 MAPK, NF-ƙB, TNF-α and AGE-RAGE binding affinity play role in the cell growth, proliferation, apoptosis inhibition and metastasis...
October 19, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29032188/genito-urinary-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatment
#14
REVIEW
Thomas Gevaert, Rodolfo Montironi, Antonio Lopez-Beltran, Geert 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. The increasing knowledge on the genomic landscape of GU cancers supports stratification of patients for targeted therapies. This review focusses on emerging biomarkers and the role of genomics in predicting clinical benefit to immunomodulatory agents in GU cancers...
October 12, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29024776/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
#15
REVIEW
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 lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens the clinical relevance of this immunological biomarker. TILs in the post-neoadjuvant residual disease setting are acquiring increasing importance as a stratifying marker in clinical trials, considering the raising interest on immunotherapeutic strategies after neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without invasive carcinoma, represent an emerging area of clinical breast cancer research...
October 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28993206/targeting-receptor-tyrosine-kinase-ephb4-in-cancer-therapy
#16
REVIEW
Yinnan Chen, Hongmei Zhang, Yanmin Zhang
Eph receptors and their Eph receptor-interacting (ephrin) ligands together form an important cell communication system with diverse roles. Experimental evidence demonstrated Eph receptor bidirectional signaling with both tumor-suppressing and tumor-promoting activities in cancer cells. The tyrosine kinase EphB4, a member of the Eph receptor family, has been associated with tumor angiogenesis, growth and metastasis, thus making it a valuable and attractive target for drug design for therapeutic applications...
October 6, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28987965/emerging-targets-in-cancer-immunotherapy
#17
REVIEW
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 additional immunomodulatory mechanisms to activate patients' own anti-tumor immune responses...
October 5, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28965871/foxo1-another-avenue-for-treating-digestive-malignancy
#18
REVIEW
Feiyu Shi, Tian Li, Zhi Liu, Kai Qu, Chengxin Shi, Yaguang Li, Qian Qin, Liang Cheng, Xin Jin, Tianyu Yu, Wencheng Di, Jianwen Que, Hongping Xia, Junjun She
Digestive malignancies are the leading cause of mortality among all neoplasms, contributing to estimated 3 million deaths in 2012 worldwide. The mortality rate hassurpassed lung cancer and prostate cancer in recent years. The transcription factor Forkhead Box O1 (FOXO1) is a key member of Forkhead Box family, regulating diverse cellular functions during tumor initiation, progression and metastasis. In this review, we focus on recent studies investigating the antineoplastic role of FOXO1 in digestive malignancy...
September 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28964938/impact-of-dna-methylation-programming-on-normal-and-pre-leukemic-hematopoiesis
#19
REVIEW
Jens Langstein, Michael D Milsom, Daniel B Lipka
Epigenome regulation is a critical mechanism that governs cell identity, lineage specification and developmental cell fates. With the advent of low-input and single-cell technologies as well as sophisticated cell labeling techniques, our understanding of transcriptional and epigenetic regulation of hematopoiesis is currently undergoing dramatic changes. Increasingly, evidence suggests that the epigenome conformation acts as a critical decision-making mechanism that instructs self-renewal, differentiation and developmental fates of hematopoietic progenitor cells...
September 27, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28962927/epigenetics-in-multiple-myeloma-from-mechanisms-to-therapy
#20
REVIEW
Mohammad Alzrigat, Alba Atienza Párraga, Helena Jernberg-Wiklund
Multiple myeloma (MM) is a tumor of antibody producing plasmablasts/plasma cells that resides within the bone marrow (BM). In addition to the well-established role of genetic lesions and tumor-microenvironment interactions in the development of MM, deregulated epigenetic mechanisms are emerging as important in MM pathogenesis. Recently, MM sequencing and expression projects have revealed that mutations and copy number variations as well as deregulation in the expression of epigenetic modifiers are characteristic features of MM...
September 26, 2017: Seminars in Cancer Biology
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