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Cancer precision medicine

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https://www.readbyqxmd.com/read/28334334/p53-and-its-mutants-on-the-slippery-road-from-stemness-to-carcinogenesis
#1
Alina Molchadsky, Varda Rotter
Normal development, tissue homeostasis and regeneration following injury rely on the proper functions of wide repertoire of stem cells (SCs) persisting during embryonic period and throughout the adult life. Therefore, SCs employ robust mechanisms to preserve their genomic integrity and avoid heritage of mutations to their daughter cells. Importantly, propagation of SCs with faulty DNA as well as dedifferentiation of genomically altered somatic cells may result in derivation of cancer SCs, which are considered to be the driving force of the tumorigenic process...
March 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28332502/consensus-molecular-subtypes-and-the-evolution-of-precision-medicine-in-colorectal-cancer
#2
Rodrigo Dienstmann, Louis Vermeulen, Justin Guinney, Scott Kopetz, Sabine Tejpar, Josep Tabernero
No abstract text is available yet for this article.
March 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28331002/personalized-in-vitro-and-in-vivo-cancer-models-to-guide-precision-medicine
#3
Chantal Pauli, Benjamin D Hopkins, Davide Prandi, Reid Shaw, Tarcisio Fedrizzi, Andrea Sboner, Verena Sailer, Michael Augello, Loredana Puca, Rachele Rosati, Terra J McNary, Yelena Churakova, Cynthia Cheung, Joanna Triscott, David Pisapia, Rema Rao, Juan Miguel Mosquera, Brian Robinson, Bishoy M Faltas, Brooke E Emerling, Vijayakrishna K Gadi, Brady Bernard, Olivier Elemento, Himisha Beltran, Francesca Demichelis, Christopher J Kemp, Carla Grandori, Lewis C Cantley, Mark A Rubin
Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial...
March 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28330821/beyond-precision-surgery-molecularly-motivated-precision-care-for-gastric-cancer
#4
REVIEW
Y Y Choi, J-H Cheong
Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Despite the high disease prevalence, gastric cancer research has not gained much attention. Recently, genome-scale technology has made it possible to explore the characteristics of gastric cancer at the molecular level. Accordingly, gastric cancer can be classified into molecular subtypes that convey more detailed information of tumor than histopathological characteristics, and these subtypes are associated with clinical outcomes...
March 1, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28328502/spatial-statistics-for-segmenting-histological-structures-in-h-e-stained-tissue-images
#5
Luong Nguyen, A Burak Tosun, Jeffrey Fine, Adrian Lee, D Lansing Taylor, Chakra Chennubhotla
Segmenting a broad class of histological structures in transmitted light and/or fluorescence-based images is a prerequisite for determining the pathological basis of cancer, elucidating spatial interactions between histological structures in tumor microenvironments (e.g. tumor infiltrating lymphocytes), facilitating precision medicine studies with deep molecular profiling, and providing an exploratory tool for pathologists. Our paper focuses on segmenting histological structures in hematoxylin and eosin (H&E) stained images of breast tissues, e...
March 16, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28325298/relevance-of-fusion-genes-in-pediatric-cancers-toward-precision-medicine
#6
REVIEW
Célia Dupain, Anne Catherine Harttrampf, Giorgia Urbinati, Birgit Geoerger, Liliane Massaad-Massade
Pediatric cancers differ from adult tumors, especially by their very low mutational rate. Therefore, their etiology could be explained in part by other oncogenic mechanisms such as chromosomal rearrangements, supporting the possible implication of fusion genes in the development of pediatric cancers. Fusion genes result from chromosomal rearrangements leading to the juxtaposition of two genes. Consequently, an abnormal activation of one or both genes is observed. The detection of fusion genes has generated great interest in basic cancer research and in the clinical setting, since these genes can lead to better comprehension of the biological mechanisms of tumorigenesis and they can also be used as therapeutic targets and diagnostic or prognostic biomarkers...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28324908/-magnetic-sentinel-lymph-node-detection-in-prostate-cancer-after-intraprostatic-injection-of-superparamagnetic-iron-oxide-nanoparticles
#7
Alexander Winter, Svenja Engels, Tobias Kowald, Tina Susanne Paulo, Holger Gerullis, Ajay Chavan, Friedhelm Wawroschek
In prostate cancer, reliable information about the lymph node status is of great importance for accurate staging and the optimal planning of treatment. Despite recent advances in imaging, the histological detection of metastases, or pelvic lymphadenectomy (PLND), continues to be the most reliable method for lymph node staging in clinically localised prostate cancer, especially as this procedure enables the detection of small or micrometastases. Radioisotope-guided sentinel PLND (sPLND) demonstrates high sensitivity in the detection of lymph node metastases as well as low morbidity in prostate cancer because of the targeted removal of a relatively small number of lymph nodes...
March 21, 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28319221/fluorescent-chemical-probes-for-accurate-tumor-diagnosis-and-targeting-therapy
#8
REVIEW
Min Gao, Fabiao Yu, Changjun Lv, Jaebum Choo, Lingxin Chen
Surgical resection of solid tumors is currently the gold standard and preferred therapeutic strategy for cancer. Chemotherapy drugs also make a significant contribution by inhibiting the rapid growth of tumor cells and these two approaches are often combined to enhance treatment efficacy. However, surgery and chemotherapy inevitably lead to severe side effects and high systemic toxicity, which in turn results in poor prognosis. Precision medicine has promoted the development of treatment modalities that are developed to specifically target and kill tumor cells...
March 20, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28318170/-application-of-saliva-in-disease-diagnosis
#9
Cheng Xingqun, Zhou Xuedong, Xu Xin
Saliva is secreted by salivary glands and performs a variety of functions, including mouth cleaning and protection, antibacterial activity, and digestion. With the rapid progress in salivaomics, saliva became recognized as a potential pool of biological markers. Being a non-invasive and safe source, saliva is a potential substitute for blood in diagnosis and prognosis of diseases. This review summarizes the latest advancement in saliva-related studies and presents the potential value of saliva in early diagnosis of oral diseases, such as dental caries, periodontal disease, cancer, diabetes, and other systemic disorders...
December 1, 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28317407/using-molecular-diagnostic-testing-to-personalize-the-treatment-of-patients-with-gastrointestinal-stromal-tumors
#10
Amber E Bannon, Lillian R Klug, Christopher L Corless, Michael C Heinrich
The diagnosis and treatment of gastrointestinal stromal tumor (GIST) has emerged as a paradigm for modern cancer treatment ("precision medicine"), as it highlights the importance of matching molecular defects with specific therapies. Over the past two decades, the molecular classification and diagnostic work up of GIST has been radically transformed, accompanied by the development of molecular therapies for specific subgroups of GIST. This review summarizes the developments in the field of molecular diagnosis of GIST, particularly as they relate to optimizing medical therapy...
March 20, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28315070/mechanisms-of-resistance-in-multiple-myeloma
#11
Athanasios Papadas, Fotis Asimakopoulos
Multiple myeloma (MM) is an incurable hematopoietic cancer that is characterized by malignant plasma cell infiltration of the bone marrow and/or extramedullary sites. Multi-modality approaches including "novel agents," traditional chemotherapy, and/or stem cell transplantation are used in MM therapy. Drug resistance, however, ultimately develops and the disease remains incurable for the vast majority of patients. In this chapter, we review both tumor cell-autonomous and non-autonomous (microenvironment-dependent) mechanisms of drug resistance...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28314784/integrative-cancer-pharmacogenomics-to-infer-large-scale-drug-taxonomy
#12
Nehme El-Hachem, Deena M A Gendoo, Laleh Soltan Ghoraie, Zhaleh Safikhani, Petr Smirnov, Christina Chung, Kenan Deng, Alisa Fang, Erin Birkwood, Chantal Ho, Ruth Isserlin, Gary Bader, Anna Goldenberg, Benjamin Haibe-Kains
Identification of drug targets and mechanism of action (MoA) for new and uncharacterized anticancer drugs is important for optimization of treatment efficacy. Current MoA prediction largely relies on prior information including side effects, therapeutic indication, and chemo-informatics. Such information is not transferable or applicable for newly identified, previously uncharacterized small molecules. Therefore, a shift in the paradigm of MoA predictions is necessary towards development of unbiased approaches that can elucidate drug relationships and efficiently classify new compounds with basic input data...
March 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28303491/changing-the-therapeutic-landscape-in-non-small-cell-lung-cancers-the-evolution-of-comprehensive-molecular-profiling-improves-access-to-therapy
#13
REVIEW
Joshua K Sabari, Fernando Santini, Isabella Bergagnini, W Victoria Lai, Kathryn C Arbour, Alexander Drilon
Targeting genomic alterations has led to a paradigm shift in the treatment of patients with lung cancer. In an effort to better identify potentially actionable alterations that may predict response to FDA-approved and or investigational therapies, many centers have migrated towards performing targeted exome sequencing in patients with stage IV disease. The implementation of next-generation sequencing (NGS) in the evaluation of tumor tissue from patients with NSCLC has led to the discovery of targetable alterations in tumors that previously had no known actionable targets by less comprehensive profiling...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28302921/deciphering-the-acute-cellular-phosphoproteome-response-to-irradiation-with-x-rays-protons-and-carbon-ions
#14
Martin Winter, Ivana Dokic, Julian Schlegel, Uwe Warnken, Jürgen Debus, Amir Abdollahi, Martina Schnölzer
Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive. Here, we present the first comprehensive proteomic and phosphoproteomic study applying stable isotope labeling by amino acids in cell culture (SILAC) in combination with high-resolution mass spectrometry to decipher cellular response to irradiation with X-rays, protons and carbon ions...
March 16, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28300714/biomarkers-and-immunotherapeutic-targets-in-glioblastoma
#15
REVIEW
Alice L Hung, Tomas Garzon-Muvdi, Michael Lim
Glioblastoma (GBM) is an aggressive central nervous system (CNS) cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides towards changing current management strategies. A diverse set of biomarkers has been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28299801/bi-allelic-alterations-in-dna-repair-genes-underpin-homologous-recombination-dna-repair-defects-in-breast-cancer
#16
Robert W Mutter, Nadeem Riaz, Charlotte K Y Ng, Rob Delsite, Salvatore Piscuoglio, Marcia Edelweiss, Luciano G Martelotto, Rita A Sakr, Tari A King, Dilip D Giri, Maria Drobnjak, Edi Brogi, Ranjit Bindra, Giana Bernheim, Raymond S Lim, Pedro Blecua, Alexis Desrichard, Dan Higginson, Russell Towers, Ruomu Jiang, William Lee, Britta Weigelt, Jorge S Reis-Filho, Simon N Powell
Homologous recombination (HR) DNA repair deficient (HRD) breast cancers have been shown to be sensitive to DNA repair targeted therapies. Burgeoning evidence suggests that sporadic breast cancers, lacking germline BRCA1/BRCA2 mutations, may also be HRD. We developed a functional ex vivo RAD51-based test to identify HRD primary breast cancers. An integrated approach examining methylation, gene expression and whole-exome sequencing was employed to ascertain the etiology of HRD. Functional HRD breast cancers displayed genomic features of lack of competent HR, including large-scale state transitions and specific mutational signatures...
March 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28299476/a-comparison-of-the-molecular-subtypes-of-triple-negative-breast-cancer-among-non-asian-and-taiwanese-women
#17
Ling-Ming Tseng, Jen-Hwey Chiu, Chun-Yu Liu, Yi-Fang Tsai, Yun-Lin Wang, Chu-Wen Yang, Yi-Ming Shyr
BACKGROUND: "Precision medicine" is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women. METHODS: GEO Datasets for non-Asian (12 groups, n = 1450) and Taiwanese (3 groups, n = 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed...
March 15, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28298516/precision-medicine-in-breast-cancer
#18
Teresa G Odle
Breast cancer care has improved markedly in recent decades, but new advancements in diagnosis and treatment depend on translating genomics and precision medicine into clinical care. This article discusses the basics of genomics, breast cancer biomarkers and subtypes, and the effects of genomic advancements on future breast cancer diagnosis, treatment, and survival. The article also presents challenges related to introducing precision medicine into cancer care and the role of imaging in breast cancer diagnosis and treatment in precision medicine...
March 2017: Radiologic Technology
https://www.readbyqxmd.com/read/28297627/clinical-and-technical-aspects-of-genomic-diagnostics-for-precision-oncology
#19
Yuri Sheikine, Frank C Kuo, Neal I Lindeman
The emergence of precision medicine has been predicated on significant recent advances in diagnostic technology, particularly the advent of next-generation sequencing (NGS). Although the chemical technology underlying NGS is complex, and the computational biology expertise required to build systems to facilely interpret the results is highly specialized, the variables involved in designing and deploying a genomic testing program for cancer can be readily understood and applied by understanding several basic considerations...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28295846/the-enigmatic-oncogene-and-tumor-suppressor-like-properties-of-rad54b-insights-into-genome-instability-and-cancer
#20
REVIEW
Erin N McAndrew, Kirk J McManus
One of the major challenges to the cell is to ensure genome stability, which can be compromised through endogenous errors or exogenous DNA damaging agents, such as ionizing radiation or common chemotherapeutic agents. To maintain genome stability the cell has a multifaceted line of defense, including cell cycle checkpoints and DNA damage repair pathways. RAD54B is involved in many of these pathways and thus exhibits a role in maintaining and repairing genome stability following DNA damage. RAD54B is involved in cell cycle regulation after DNA damage and participates in homologous recombinational repair, which ensures the precise repair of the most deleterious DNA lesions, double-stranded breaks...
March 13, 2017: Genes, Chromosomes & Cancer
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