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Oncogene addiction

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https://www.readbyqxmd.com/read/29153859/oligoprogressive-oncogene-addicted-lung-tumours-does-stereotactic-body-radiotherapy-have-a-role-introducing-the-halt-trial
#1
EDITORIAL
F McDonald, G G Hanna
No abstract text is available yet for this article.
November 16, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29138515/targeting-a-non-oncogene-addiction-to-the-atr-chk1-axis-for-the-treatment-of-small-cell-lung-cancer
#2
Fabian Doerr, Julie George, Anna Schmitt, Filippo Beleggia, Tim Rehkämper, Sarah Hermann, Vonn Walter, Jean-Philip Weber, Roman K Thomas, Maike Wittersheim, Reinhard Büttner, Thorsten Persigehl, H Christian Reinhardt
Small cell lung cancer (SCLC) is a difficult to treat subtype of lung cancer. One of the hallmarks of SCLC is its almost uniform chemotherapy sensitivity. However, chemotherapy response is typically transient and patients frequently succumb to SCLC within a year following diagnosis. We performed a transcriptome analysis of the major human lung cancer entities. We show a significant overexpression of genes involved in the DNA damage response, specifically in SCLC. Particularly CHEK1, which encodes for the cell cycle checkpoint kinase CHK1, is significantly overexpressed in SCLC, compared to lung adenocarcinoma...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29128428/clinical-and-translational-implications-of-ret-rearrangements-in-non-small-cell-lung-cancer
#3
REVIEW
Roberto Ferrara, Nathalie Auger, Edouard Auclin, Benjamin Besse
Since the discovery in 2012 of RET rearrangements in non-small cell lung cancer (NSCLC), at least 12 different fusion variants have been identified, with KIF5B-RET being the most frequent and the best characterized. Unlike ALK and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry, although fluorescence in situ hybridization and reverse transcriptase PCR are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histology, never-smoking status, younger age, more advanced stage disease, potentially higher chemo-sensitivity (in particular to pemetrexed-based regimens), and coexistence of other genomic alterations...
November 8, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29125118/research-advances-of-calcium-and-integrin-binding-protein-1-in-tumors
#4
Ling Hui, Fang Wang
Calcium-and integrin-binding protein 1(CIB1),a member of calcium binding protein containing EF-hand domain,has been shown to bind a variety of signaling proteins. Interaction of CIB1 with its various binding partners provides valuable insight into potential mechanisms by which CIB1 may regulate diverse tumors characteristic biological process that range from adhesion,migration,cell survival,proliferation,and angiogenesis. CIB1 has also been implicated in both the increase and decrease of cell proliferation...
October 30, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29118813/the-leukemic-stem-cell-niche-adaptation-to-hypoxia-versus-oncogene-addiction
#5
Giulia Cheloni, Martina Poteti, Silvia Bono, Erico Masala, Nathalie M Mazure, Elisabetta Rovida, Matteo Lulli, Persio Dello Sbarba
Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC). The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN) are placed in tissue areas at the lower end of this range ("hypoxic" SCN), to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29107960/glutamine-deficiency-induces-dna-alkylation-damage-and-sensitizes-cancer-cells-to-alkylating-agents-through-inhibition-of-alkbh-enzymes
#6
Thai Q Tran, Mari B Ishak Gabra, Xazmin H Lowman, Ying Yang, Michael A Reid, Min Pan, Timothy R O'Connor, Mei Kong
Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death...
November 2017: PLoS Biology
https://www.readbyqxmd.com/read/29107170/cellular-and-molecular-mechanisms-underlying-planar-cell-polarity-pathway-contributions-to-cancer-malignancy
#7
REVIEW
Kaceauy VanderVorst, Jason Hatakeyama, Anastasia Berg, Hyun Lee, Kermit L Carraway
While the mutational activation of oncogenes drives tumor initiation and growth by promoting cellular transformation and proliferation, increasing evidence suggests that the subsequent re-engagement of largely dormant developmental pathways contributes to cellular phenotypes associated with the malignancy of solid tumors. Genetic studies from a variety of model organisms have defined many of the components that maintain epithelial planar cell polarity (PCP), or cellular polarity in the axis orthogonal to the apical-basal axis...
October 26, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29077093/why-do-bcl-2-inhibitors-work-and-where-should-we-use-them-in-the-clinic
#8
REVIEW
Joan Montero, Antony Letai
Intrinsic apoptosis is controlled by the BCL-2 family of proteins but the complexity of intra-family interactions makes it challenging to predict cell fate via standard molecular biology techniques. We discuss BCL-2 family regulation and how to determine cells' readiness for apoptosis and anti-apoptotic dependence. Cancer cells often adopt anti-apoptotic defense mechanisms in response to oncogenic stress or anti-cancer therapy. However, by determining their anti-apoptotic addiction, we can use novel BH3 mimetics to overwhelm this apoptotic blockade...
October 27, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29072187/substance-abuse-and-cancer
#9
G I Moussas, A G Papadopoulou
Substance abuse is a health problem with serious psychological and psychiatric dimensions and multiple social and economic consequences. Cancer is a disease that threatens not only life and physical integrity but mental health as well. Oncology patients suffer from mental disorders in high rates, especially from depression and anxiety. The role of substance abuse in the pathogenesis of cancer is studied systematically, since there are research data supporting the mutagenic effects of certain substances. It has been supported that a possible dysregulation of the immune system is linked to the oncogenic processes induced by substances of abuse...
July 2017: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/28975081/radiotherapy-for-oligometastatic-lung-cancer
#10
REVIEW
Derek P Bergsma, Joseph K Salama, Deepinder P Singh, Steven J Chmura, Michael T Milano
Non-small cell lung cancer (NSCLC) typically presents at an advanced stage, which is often felt to be incurable, and such patients are usually treated with a palliative approach. Accumulating retrospective and prospective clinical evidence, including a recently completed randomized trial, support the existence of an oligometastatic disease state wherein select individuals with advanced NSCLC may experience historically unprecedented prolonged survival with aggressive local treatments, consisting of radiotherapy and/or surgery, to limited sites of metastatic disease...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28969692/role-of-protein-kinases-ck1%C3%AE-and-ck2-in-multiple-myeloma-regulation-of-pivotal-survival-and-stress-managing-pathways
#11
REVIEW
Sabrina Manni, Marilena Carrino, Francesco Piazza
Multiple myeloma (MM) is a malignant tumor of transformed plasma cells. MM pathogenesis is a multistep process. This cancer can occur de novo (rarely) or it can develop from monoclonal gammopathy of undetermined significance (most of the cases). MM can be asymptomatic (smoldering myeloma) or clinically active. Malignant plasma cells exploit intrinsic and extrinsic bone marrow microenvironment-derived growth signals. Upregulation of stress-coping pathways is also instrumental to maintain MM cell growth. The phylogenetically related Ser/Thr kinases CSNK1A1 (CK1α) and CSNK2 (CK2) have recently gained a growing importance in hematologic malignancies arising both from precursors and from mature blood cells...
October 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28951131/targeting-copz1-non-oncogene-addiction-counteracts-the-viability-of-thyroid-tumor-cells
#12
Maria Chiara Anania, Elena Cetti, Daniele Lecis, Katia Todoerti, Alessandro Gulino, Giuseppe Mauro, Tiziana Di Marco, Loredana Cleris, Sonia Pagliardini, Giacomo Manenti, Beatrice Belmonte, Claudio Tripodo, Antonino Neri, Angela Greco
Thyroid carcinoma is generally associated with good prognosis, but no effective treatments are currently available for aggressive forms not cured by standard therapy. To find novel therapeutic targets for this tumor type, we had previously performed a siRNA-based functional screening to identify genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same extent for the viability of normal cells (non-oncogene addiction paradigm). Among those, we found the coatomer protein complex ζ1 (COPZ1) gene, which is involved in intracellular traffic, autophagy and lipid homeostasis...
September 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28944080/predicting-ligand-dependent-tumors-from-multi-dimensional-signaling-features
#13
Helge Hass, Kristina Masson, Sibylle Wohlgemuth, Violette Paragas, John E Allen, Mark Sevecka, Emily Pace, Jens Timmer, Joerg Stelling, Gavin MacBeath, Birgit Schoeberl, Andreas Raue
Targeted therapies have shown significant patient benefit in about 5-10% of solid tumors that are addicted to a single oncogene. Here, we explore the idea of ligand addiction as a driver of tumor growth. High ligand levels in tumors have been shown to be associated with impaired patient survival, but targeted therapies have not yet shown great benefit in unselected patient populations. Using an approach of applying Bagged Decision Trees (BDT) to high-dimensional signaling features derived from a computational model, we can predict ligand dependent proliferation across a set of 58 cell lines...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28918056/the-therapeutic-potential-of-crispr-cas9-systems-in-oncogene-addicted-cancer-types-virally-driven-cancers-as-a-model-system
#14
REVIEW
Luqman Jubair, Nigel A J McMillan
The field of gene editing is undergoing unprecedented growth. The first ex vivo human clinical trial in China started in 2016, more than 1000 US patents have been filed, and there is exponential growth in publications. The ability to edit genes with high fidelity is promising for the development of new treatments for a range of diseases, particularly inherited conditions, infectious diseases, and cancers. For cancer, a major issue is the identification of driver mutations and oncogenes to target for therapeutic effect, and this requires the development of robust models with which to prove their efficacy...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28898697/chronic-cigarette-smoke-induced-epigenomic-changes-precede-sensitization-of-bronchial-epithelial-cells-to-single-step-transformation-by-kras-mutations
#15
Michelle Vaz, Stephen Y Hwang, Ioannis Kagiampakis, Jillian Phallen, Ashwini Patil, Heather M O'Hagan, Lauren Murphy, Cynthia A Zahnow, Edward Gabrielson, Victor E Velculescu, Hariharan P Easwaran, Stephen B Baylin
We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28893801/galectin-3-a-druggable-vulnerability-for-kras-addicted-cancers
#16
Laetitia Seguin, Maria F Camargo, Hiromi I Wettersten, Shumei Kato, Jay S Desgrosellier, Tami von Schalscha, Kathryn C Elliott, Erika Cosset, Jacqueline Lesperance, Sara M Weis, David A Cheresh
Identifying the molecular basis for cancer cell dependence on oncogenes such as KRAS can provide new opportunities to target these addictions. Here, we identify a novel role for the carbohydrate-binding protein Galectin-3 as a lynchpin for KRAS dependence. By directly binding to the cell surface receptor integrin αvβ3, Galectin-3 gives rise to KRAS addiction by enabling multiple functions of KRAS in anchorage-independent cells, including formation of macropinosomes that facilitate nutrient uptake and ability to maintain redox balance...
September 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28881369/-molecular-pathogenesis-of-thyroid-nodules-relevance-for-clinical-care
#17
D Führer, T Musholt, K W Schmid
Thyroid nodules represent heterogeneous tumors with distinct molecular signatures. While benign thyroid nodules correspond to poly- or monoclonal tumors, thyroid carcinomas are monoclonal and thus "real" neoplasms. These are caused by somatic mutations that lead to the constitutive activation of specific signaling cascades and determine the corresponding histology and also partly the functional phenotype of the thyroid tumor. Dedifferentiation of thyroid carcinomas is accompanied by the occurrence of additional mutations in the tumors...
September 2017: Laryngo- Rhino- Otologie
https://www.readbyqxmd.com/read/28869494/-dicing-and-splicing-sphingosine-kinase-and-relevance-to-cancer
#18
REVIEW
Nahal Haddadi, Yiguang Lin, Ann M Simpson, Najah T Nassif, Eileen M McGowan
Sphingosine kinase (SphK) is a lipid enzyme that maintains cellular lipid homeostasis. Two SphK isozymes, SphK1 and SphK2, are expressed from different chromosomes and several variant isoforms are expressed from each of the isozymes, allowing for the multi-faceted biological diversity of SphK activity. Historically, SphK1 is mainly associated with oncogenicity, however in reality, both SphK1 and SphK2 isozymes possess oncogenic properties and are recognized therapeutic targets. The absence of mutations of SphK in various cancer types has led to the theory that cancer cells develop a dependency on SphK signaling (hyper-SphK signaling) or "non-oncogenic addiction"...
September 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28843992/tracking-met-de-addiction-in-lung-cancer-a-road-towards-the-oncogenic-target
#19
REVIEW
S Pilotto, L Carbognin, N Karachaliou, P C Ma, R Rosell, G Tortora, E Bria
The discovery of druggable oncogenic drivers (i.e. EGFR and ALK), along with the introduction of comprehensive tumor genotyping techniques into the daily clinical practice define non-small-cell lung cancer (NSCLC) asa group of heterogeneous diseases, requiring a context-personalized clinico-therapeutical approach. Among the most investigated biomarkers, the MET proto-oncogene has been extensively demonstrated to play a crucial role throughout the lung oncogenesis, unbalancing the proliferation/apoptosis signaling and influencing the epithelial-mesenchymal transition and the invasive phenotype...
November 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28843358/baseline-and-on-treatment-characteristics-of-serum-tumor-markers-in-stage-iv-oncogene-addicted-adenocarcinoma-of-the-lung
#20
Sinead A Noonan, Tejas Patil, Dexiang Gao, Gentry G King, Jessica R Thibault, Xian Lu, Paul A Bunn, Robert C Doebele, W Thomas Purcell, Anna E Barón, D Ross Camidge
INTRODUCTION: The role of serum tumor markers in the modern management of advanced NSCLC remains poorly described. METHODS: A single-center retrospective analysis of available carcinoembryonic antigen, CA125, CA19.9, and CA27.29 levels at baseline and during treatment of stage IV lung adenocarcinoma by oncogenic driver was conducted. RESULTS: A total of 142 patients were analyzed (60 with anaplastic lymphoma kinase gene [ALK] rearrangement, 50 with EGFR mutation, four with ROS1 rearrangement, and 29 with KRAS mutation)...
August 24, 2017: Journal of Thoracic Oncology
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