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Cancer precision medicine

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https://www.readbyqxmd.com/read/28822237/beyond-genomics-targeting-the-epigenome-in-diffuse-large-b-cell-lymphoma
#1
REVIEW
Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced...
August 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28819565/genomic-and-immune-heterogeneity-are-associated-with-differential-responses-to-therapy-in-melanoma
#2
Alexandre Reuben, Christine N Spencer, Peter A Prieto, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, John P Miller, Xizeng Mao, Mariana Petaccia De Macedo, Jiong Chen, Xingzhi Song, Hong Jiang, Pei-Ling Chen, Hannah C Beird, Haven R Garber, Whijae Roh, Khalida Wani, Eveline Chen, Cara Haymaker, Marie-Andrée Forget, Latasha D Little, Curtis Gumbs, Rebecca L Thornton, Courtney W Hudgens, Wei-Shen Chen, Jacob Austin-Breneman, Robert Szczepaniak Sloane, Luigi Nezi, Alexandria P Cogdill, Chantale Bernatchez, Jason Roszik, Patrick Hwu, Scott E Woodman, Lynda Chin, Hussein Tawbi, Michael A Davies, Jeffrey E Gershenwald, Rodabe N Amaria, Isabella C Glitza, Adi Diab, Sapna P Patel, Jianhua Hu, Jeffrey E Lee, Elizabeth A Grimm, Michael T Tetzlaff, Alexander J Lazar, Ignacio I Wistuba, Karen Clise-Dwyer, Brett W Carter, Jianhua Zhang, P Andrew Futreal, Padmanee Sharma, James P Allison, Zachary A Cooper, Jennifer A Wargo
Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28818953/new-horizons-for-precision-medicine-in-biliary-tract-cancers
#3
REVIEW
Juan W Valle, Angela Lamarca, Lipika Goyal, Jorge Barriuso, Andrew X Zhu
Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e...
August 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28818916/a-pathology-atlas-of-the-human-cancer-transcriptome
#4
Mathias Uhlen, Cheng Zhang, Sunjae Lee, Evelina Sjöstedt, Linn Fagerberg, Gholamreza Bidkhori, Rui Benfeitas, Muhammad Arif, Zhengtao Liu, Fredrik Edfors, Kemal Sanli, Kalle von Feilitzen, Per Oksvold, Emma Lundberg, Sophia Hober, Peter Nilsson, Johanna Mattsson, Jochen M Schwenk, Hans Brunnström, Bengt Glimelius, Tobias Sjöblom, Per-Henrik Edqvist, Dijana Djureinovic, Patrick Micke, Cecilia Lindskog, Adil Mardinoglu, Fredrik Ponten
Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation...
August 18, 2017: Science
https://www.readbyqxmd.com/read/28816646/chronic-cigarette-smoke-mediated-global-changes-in-lung-mucoepidermoid-cells-a-phosphoproteomic-analysis
#5
Hitendra S Solanki, Jayshree Advani, Aafaque Ahmad Khan, Aneesha Radhakrishnan, Nandini A Sahasrabuddhe, Sneha M Pinto, Xiaofei Chang, Thottethodi Subrahmanya Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee
Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#6
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28810144/integrated-genomic-characterization-of-pancreatic-ductal-adenocarcinoma
#7
(no author information available yet)
We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28807936/genomic-alterations-in-circulating-tumor-dna-from-diverse-cancer-patients-identified-by-next-generation-sequencing
#8
Maria Schwaederle, Ranajoy Chattopadhyay, Shumei Kato, Paul T Fanta, Kimberly C Banks, In Sil Choi, David E Piccioni, Sadakatsu Ikeda, AmirAli Talasaz, Richard B Lanman, Lyudmila Bazhenova, Razelle Kurzrock
Non-invasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort <p>of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers.</p> The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%) or lung (20.7%). ctDNA obtained from most patients (N = 423 (63%)) displayed at least 1 alteration...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28807841/racial-disparity-in-gastrointestinal-cancer-risk
#9
REVIEW
Hassan Ashktorab, Sonia S Kupfer, Hassan Brim, John M Carethers
Cancer from the gastrointestinal tract and its associated excretory organs will occur in over 300,000 Americans in 2017, with colorectal cancer responsible for over forty percent of that burden; there will be over 150,000 deaths from this group of cancers in the same time period. Disparities among subgroups related to these cancers' incidence and mortality exist. The epidemiology and risk factors associated with each cancer bear out differences for racial groups in the United States. Esophageal adenocarcinoma is more frequent in Non-Hispanic Whites, whereas esophageal squamous cell carcinoma with risk factors of tobacco and alcohol is more frequent among Blacks...
August 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28807365/-the-breakthrough-of-personalized-medicine-new-hopes-and-new-challenges
#10
REVIEW
Ronan Flippot, Christophe Massard, Edouard Auclin, David Azria, Héloïse Bourien, Philippe Rochigneux, Antoine Schernberg, Loïc Verlingue, Lara Zafrani, Stéphane Vignot
The development of personalized medicine in oncology is based on biomarkers that help select populations for more efficient and less toxic therapies. The onset of molecular biology led to new paradigms in drug development, with efficacy data reported in early clinical trials and accelerated approvals. Multiple clinical trials, including SHIVA, SAFIR-01 and MOSCATO-01, have been developed to evaluate the interest of treatment decision-making based on tumor molecular profiling, with the ambition to replace historical clinical and pathological classifications...
August 11, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28807210/personalized-treatment-in-patients-with-colorectal-liver-metastases
#11
Dimitrios Moris, Timothy M Pawlik
BACKGROUND: Precision Medicine Initiative is a new research effort aiming to offer personalized treatment in many diseases, including cancer. The aim of the present article is to offer novel insights about the role of personalized treatment in patients with colorectal liver metastases (CRLM). METHODS: A review of the literature regarding personalized medicine and colorectal liver metastases was performed mainly in the MEDLINE/PubMed database. RESULTS: Surgical resection remains the only hope for cure of CRLM...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28806950/precision-medicine-approaches-to-lung-adenocarcinoma-with-concomitant-met-and-her2-amplification
#12
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
BACKGROUND: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models. METHODS: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28796828/acid-free-glyoxal-as-a-substitute-of-formalin-for-structural-and-molecular-preservation-in-tissue-samples
#13
Gianni Bussolati, Laura Annaratone, Enrico Berrino, Umberto Miglio, Mara Panero, Marco Cupo, Patrizia Gugliotta, Tiziana Venesio, Anna Sapino, Caterina Marchiò
Tissue fixation in phosphate buffered formalin (PBF) remains the standard procedure in histopathology, since it results in an optimal structural, antigenic and molecular preservation that justifies the pivotal role presently played by diagnoses on PBF-fixed tissues in precision medicine. However, toxicity of formaldehyde causes an environmental concern and may demand substitution of this reagent. Having observed that the reported drawbacks of commercially available glyoxal substitutes of PBF (Prefer, Glyo-fix, Histo-Fix, Histo-CHOICE, and Safe-Fix II) are likely related to their acidity, we have devised a neutral fixative, obtained by removing acids from the dialdehyde glyoxal with an ion-exchange resin...
2017: PloS One
https://www.readbyqxmd.com/read/28794807/prognostic-and-predictive-biomarkers-in-prostate-cancer-latest-evidence-and-clinical-implications
#14
REVIEW
Naoki Terada, Shusuke Akamatsu, Takashi Kobayashi, Takahiro Inoue, Osamu Ogawa, Emmanuel S Antonarakis
Advances in our understanding of the mechanisms driving castration-resistant prostate cancer have promoted the development of several new drugs including androgen receptor-directed therapy and chemotherapy. Concomitant docetaxel treatment at the beginning of hormonal therapy for metastatic prostate cancer has resulted in longer overall survival than with hormonal therapy alone. Elucidating an appropriate treatment sequence using these therapies is important for maximizing clinical benefit in castration-sensitive and castration-resistant prostate cancer patients...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28770623/angiogenesis-inhibitors-in-early-development-for-gastric-cancer
#15
Mauricio P Pinto, Gareth I Owen, Ignacio Retamal, Marcelo Garrido
Angiogenesis, or the generation of new blood vessels from pre-existent ones is a critical process for tumor growth and progression. Hence, the development of angiogenesis inhibitors with therapeutic potential has been a central focus for researchers. Most angiogenesis inhibitors target the Vascular Endothelial Growth Factor (VEGF) pathway, however a number of tyrosine kinase inhibitors (TKIs), immunomodulatory drugs (IMiDs) and inhibitors of the mammalian Target-Of-Rapamycin (mTOR) pathway also display antiangiogenic activity...
August 14, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28768489/improved-anticancer-drug-response-prediction-in-cell-lines-using-matrix-factorization-with-similarity-regularization
#16
Lin Wang, Xiaozhong Li, Louxin Zhang, Qiang Gao
BACKGROUND: Human cancer cell lines are used in research to study the biology of cancer and to test cancer treatments. Recently there are already some large panels of several hundred human cancer cell lines which are characterized with genomic and pharmacological data. The ability to predict drug responses using these pharmacogenomics data can facilitate the development of precision cancer medicines. Although several methods have been developed to address the drug response prediction, there are many challenges in obtaining accurate prediction...
August 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28766239/transcriptome-modeling-and-phenotypic-assays-for-cancer-precision-medicine
#17
REVIEW
Euna Jeong, Sung Ung Moon, Mee Song, Sukjoon Yoon
Cancer precision medicine requires clinically actionable biomarkers for patient stratification and a better prediction of clinical outcome. Although thousands of cancer-enriched mutated genes have been reported by global sequencing projects, to date, only a few oncogenic mutations have been confirmed as effective biomarkers in cancer therapies. The low frequency and varied profile (i.e., allele frequency, mutation position) of mutant genes among cancer types limit the utility of predictive biomarkers. The recent explosion of cancer transcriptome and phenotypic screening data provides another opportunity for finding transcript-level biomarkers and targets, thus overcoming the limitation of cancer mutation analyses...
August 1, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28765583/liver-cancer-translating-omics-results-into-precision-medicine-for-hepatocellular-carcinoma
#18
Daniela Sia, Josep M Llovet
No abstract text is available yet for this article.
August 2, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28765336/new-directions-in-cancer-control-and-population-sciences
#19
Robert A Hiatt
Cancer control science has been evolving since it first became a focus for cancer research and program activities a century ago. The evolution of the field has responded to historical megatrends along the way that keep it relevant to the cancer-related needs of society. This commentary describes some of the key trends and developments now influencing cancer control and population sciences that reflect societal change and new tools and concepts in modern biomedical science. New directions include the impact of climate change, health care delivery research, the growth of population health science, data science, precision medicine, data sharing, implementation science, and new technologies, including social media and new geospatial methodologies...
August 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28761742/implementing-precision-cancer-medicine-in-the-public-health-services-of-norway-the-diagnostic-infrastructure-and-a-cost-estimate
#20
Anne Hansen Ree, Hege G Russnes, Daniel Heinrich, Svein Dueland, Kjetil Boye, Vigdis Nygaard, Laxmi Silwal-Pandit, Olga Østrup, Eivind Hovig, Vegard Nygaard, Einar A Rødland, Sigve Nakken, Janne T Øien, Christin Johansen, Inger R Bergheim, Veronica Skarpeteig, Menaka Sathermugathevan, Torill Sauer, Marius Lund-Iversen, Klaus Beiske, Salah Nasser, Lars Julsrud, Claudius H Reisse, Espen A Ruud, Vivi Ann Flørenes, Kirsten T Hagene, Eline Aas, Hilde Lurås, Siv Johnsen-Soriano, Gry A Geitvik, Ole Christian Lingjærde, Anne-Lise Børresen-Dale, Gunhild M Mælandsmo, Kjersti Flatmark
OBJECTIVE: Through the conduct of an individual-based intervention study, the main purpose of this project was to build and evaluate the required infrastructure that may enable routine practice of precision cancer medicine in the public health services of Norway, including modelling of costs. METHODS: An eligible patient had end-stage metastatic disease from a solid tumour. Metastatic tissue was analysed by DNA sequencing, using a 50-gene panel and a study-generated pipeline for analysis of sequence data, supplemented with fluorescence in situ hybridisation to cover relevant biomarkers...
2017: ESMO Open
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