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Cancer precision medicine

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https://www.readbyqxmd.com/read/28448782/amcp-partnership-forum-driving-value-and-outcomes-in-oncology
#1
(no author information available yet)
Innovation in cancer treatment has provided a wealth of recently available therapeutic agents and a healthy drug pipeline that promises to change the way we approach this disease and the lives of those affected in the years to come. However, the majority of these new agents, many of which are targeted to specific genomic features of various tumors, may challenge the health care system's ability to afford cancer care. This innovation drives the need to focus on the value of the treatments provided to patients with cancer and on methods to optimize the efficiency of the dollars we spend, in addition to the clinical value itself...
May 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28444967/co-delivery-of-microrna-21-antisense-oligonucleotides-and-gemcitabine-using-nanomedicine-for-pancreatic-cancer-therapy
#2
Yaqing Li, Yinting Chen, Jiajia Li, Zuoquan Zhang, Chumei Huang, Guoda Lian, Kege Yang, Shaojie Chen, Ying Lin, Lingyun Wang, Kaihong Huang, Linjuan Zeng
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining down-regulation of target genes with chemotherapy drugs, is expected to improve the therapeutic effects. Therefore, we developed a combined therapy of microRNA-21 antisense oligonucleotides (ASO-miR-21) and Gemcitabine (Gem) using a targeted co-delivery nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28443282/imprecision-in-the-era-of-precision-medicine-in-non-small-cell-lung-cancer
#3
REVIEW
Raghav Sundar, Maxime Chénard-Poirier, Dearbhaile Catherine Collins, Timothy A Yap
Over the past decade, major advances have been made in the management of advanced non-small cell lung cancer (NSCLC). There has been a particular focus on the identification and targeting of putative driver aberrations, which has propelled NSCLC to the forefront of precision medicine. Several novel molecularly targeted agents have now achieved regulatory approval, while many others are currently in late-phase clinical trial testing. These antitumor therapies have significantly impacted the clinical outcomes of advanced NSCLC and provided patients with much hope for the future...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28439535/a-murine-preclinical-syngeneic-transplantation-model-for-breast-cancer-precision-medicine
#4
Lorenzo Federico, Zechen Chong, Dong Zhang, Daniel J McGrail, Wei Zhao, Kang Jin Jeong, Christopher P Vellano, Zhenlin Ju, Mihai Gagea, Shuying Liu, Shreya Mitra, Jennifer B Dennison, Philip L Lorenzi, Robert Cardnell, Lixia Diao, Jing Wang, Yiling Lu, Lauren A Byers, Charles M Perou, Shiaw-Yih Lin, Gordon B Mills
We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28439188/next-generation-sequencing-reveals-high-prevalence-of-brca1-and-brca2-variants-of-unknown-significance-in-early-onset-breast-cancer-in-african-american-women
#5
Luisel Ricks-Santi, J Tyson McDonald, Bert Gold, Michael Dean, Nicole Thompson, Muneer Abbas, Bradford Wilson, Yasmine Kanaan, Tammey J Naab, Georgia Dunston
BACKGROUND: Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. METHODS: In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer...
2017: Ethnicity & Disease
https://www.readbyqxmd.com/read/28436954/optimized-expression-based-microdissection-of-formalin-fixed-lung-cancer-tissue
#6
Markus Grafen, Thurid R Hofmann, Andreas H Scheel, Julia Beck, Alexander Emmert, Stefan Küffer, Bernhard C Danner, Ekkehard Schütz, Reinhardt Büttner, Andreas Ostendorf, Philipp Ströbel, Hanibal Bohnenberger
Analysis of specific DNA alterations in precision medicine of tumors is crucially important for molecular targeted treatments. Lung cancer is a prototypic example and one of the leading causes of cancer-related deaths worldwide. One major technical problem of detecting DNA alterations in tissue samples is cellular heterogeneity, that is, mixture of tumor and normal cells. Microdissection is an important tool to enrich tumor cells from heterogeneous tissue samples. However, conventional laser capture microdissection has several disadvantages like user-dependent selection of regions of interest (ROI), high costs for dissection systems and long processing times...
April 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#7
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 19, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28431457/precision-medicine-and-pharmacogenetics-what-does-oncology-have-that-addiction-medicine-does-not
#8
Henry R Kranzler, Rachel V Smith, Robert Schnoll, Afaf Moustafa, Emma Greenstreet-Akman
BACKGROUND AND AIMS: Precision, personalized or stratified medicine, which promises to deliver the right treatment to the right patient, is a topic of international interest in both the lay press and the scientific literature. A key aspect of precision medicine is the identification of biomarkers that predict the response to medications (i.e. pharmacogenetics). We examined why, despite the great strides that have been made in biomarker identification in many areas of medicine, only in oncology has there been substantial progress in their clinical implementation...
April 21, 2017: Addiction
https://www.readbyqxmd.com/read/28430862/how-health-related-quality-of-life-assessment-should-be-used-in-advanced-colorectal-cancer-clinical-trials
#9
F Bonnetain, C Borg, R R Adams, J A Ajani, A Benson, H Bleiberg, B Chibaudel, E Diaz-Rubio, J Y Douillard, C S Fuchs, B J Giantonio, R Goldberg, V Heinemann, M Koopman, R Labianca, A K Larsen, T Maughan, E Mitchell, M Peeters, C J A Punt, H J Schmoll, C Tournigand, A de Gramont
Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival (OS) and more recently tumor-based endpoints such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical endpoints in current situation if such endpoints were no validated as surrogate of OS to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported endpoints that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based endpoints...
April 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28430586/epidermal-growth-factor-receptor-egfr-a-rising-star-in-the-era-of-precision-medicine-of-lung-cancer
#10
REVIEW
Xiaomin Liu, Ping Wang, Caiyan Zhang, Zhongliang Ma
Lung cancer is a leading cause of cancer mortality worldwide. In tumors, the important role of noncoding RNA regulatory networks has been more and more reveal. EGFR has been identified as an oncogenic driver of NSCLC, especially activating mutations EGFR and its inhibition with specific TKIs can generate dramatic tumor responses. Studies have shown that EGFR plays significant roles in the progression of NSCLC. Subset analysis of the small proportion of patients with EGFR-mutant lung cancer showed a disease-free survival benefit, but was underpowered to detect a survival advantage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430339/characterization-of-a-rare-nonpathogenic-sequence-variant-c-1905c-t-of-the-dihydropyrimidine-dehydrogenase-gene-dpyd
#11
Raffaele Palmirotta, Domenica Lovero, Erica Silvestris, Claudia Carella, Claudia Felici, Davide Quaresmini, Paola Cafforio, Franco Silvestris
BACKGROUND: In the era of precision medicine, the suitability of fluoropyrimidine therapies in clinical oncology can be checked by pharmacogenetic investigations of single patients, thus optimizing resources and indicating the appropriate drugs to personalize their chemotherapy. For example, the presence of dihydropyrimidine dehydrogenase gene (DPYD) polymorphisms in cancer patients may lead to adverse effects when adopting fluoropyrimidine-based therapies. METHODS: We detected in a cancer patient a rare germline synonymous heterozygous variant of DPYD (c...
April 11, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28427525/precision-medicine-for-early-breast-cancer-radiotherapy-opening-up-new-horizons
#12
REVIEW
Jacques Bernier
So far most efforts put forth to test the value of predictive and prognostic tools in the field of breast radiotherapy remained globally disappointing, or at least below the convincing levels reached for systemic therapy. Nevertheless the addition of predictive tools to the clinical armament tends to prevail over the use of the sole prognostic factors, also in radiotherapy. A number of predictive assays, clinically validated or not, have recently elicited significant associations between molecular profiles and tumor biological aggressiveness and/or radiosensitivity levels...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426279/combination-of-gemcitabine-and-docetaxel-regress-both-gastric-leiomyosarcoma-proliferation-and-invasion-in-an-imageable-patient-derived-orthotopic-xenograft-ipdox-model
#13
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Scott D Nelson, Sarah M Dry, Yunfeng Li, Tara A Russell, Arun S Singh, Bartosz Chmielowski, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
Gastric leiomyosarcoma is a recalcitrant cancer and chemotherapy strategy is controversial. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of gastric leiomyosarcoma to identify an effective therapeutic regimen in order to develop individualized precision medicine for this disease. A gastric leiomyosarcoma obtained from a patient was first grown in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP) in order to stably label the tumor stroma. The RFP-expressing tumor was then passaged orthotopically in the gastric wall of non-transgenic nude mice to establish an imageable PDOX (iPDOX) model...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28423702/experience-with-precision-genomics-and-tumor-board-indicates-frequent-target-identification-but-barriers-to-delivery
#14
Alan H Bryce, Jan B Egan, Mitesh J Borad, A Keith Stewart, Grzegorz S Nowakowski, Asher Chanan-Khan, Mrinal M Patnaik, Stephen M Ansell, Michaela S Banck, Steven I Robinson, Aaron S Mansfield, Eric W Klee, Gavin R Oliver, Jennifer B McCormick, Norine E Huneke, Colleen M Tagtow, Robert B Jenkins, Kandelaria M Rumilla, Sarah E Kerr, Jean-Pierre A Kocher, Scott A Beck, Martin E Fernandez-Zapico, Gianrico Farrugia, Konstantinos N Lazaridis, Robert R McWilliams
BACKGROUND: The ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM). RESULTS: Prior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists. Therapeutically actionable mutations were identified in 65% (92/141) of the patients tested with 32% (29/92) receiving genomically targeted therapy with FDA approved drugs or in an independent clinical trial with 45% (13/29) responding...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423659/targeting-hox-pbx-dimers-in-cancer
#15
REVIEW
Richard Morgan, Mohamed El-Tanani, Keith D Hunter, Kevin J Harrington, Hardev S Pandha
The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423591/pik3ca-mutation-and-colorectal-cancer-precision-medicine
#16
Tsuyoshi Hamada, Jonathan A Nowak, Shuji Ogino
No abstract text is available yet for this article.
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422313/regulome-networks-and-mutational-landscape-in-liver-cancer-an-informative-path-to-precision-medicine
#17
Song Yi, Nidhi Sahni
No abstract text is available yet for this article.
April 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28420618/research-progress-on-liquid-biopsy-in-oncology-and-its-clinical-applications
#18
Wang Chen, Li Yanming, Fang Xiangdong
Liquid biopsy is an emerging and promising detection tool for cancer, with the benefit of being non-invasive and convenient. It analyzes tumor-derived information in the blood or other body fluids including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and exosomes. Nowadays, with the expansion of liquid biopsy research contents and the development of capture and detection technologies, liquid biopsy is increasingly utilized in clinical applications, promoting the development of tumor precision medicine...
March 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28417948/erbb-family-signalling-a-paradigm-for-oncogene-addiction-and-personalized-oncology
#19
REVIEW
Nico Jacobi, Rita Seeboeck, Elisabeth Hofmann, Andreas Eger
ErbB family members represent important biomarkers and drug targets for modern precision therapy. They have gained considerable importance as paradigms for oncoprotein addiction and personalized medicine. This review summarizes the current understanding of ErbB proteins in cell signalling and cancer and describes the molecular rationale of prominent cases of ErbB oncoprotein addiction in different cancer types. In addition, we have highlighted experimental technologies for the development of innovative cancer cell models that accurately predicted clinical ErbB drug efficacies...
April 12, 2017: Cancers
https://www.readbyqxmd.com/read/28415793/clinical-framework-for-next-generation-sequencing-based-analysis-of-treatment-predictive-mutations-and-multiplexed-gene-fusion-detection-in-non-small-cell-lung-cancer
#20
Kajsa Ericson Lindquist, Anna Karlsson, Per Levéen, Hans Brunnström, Christel Reuterswärd, Karolina Holm, Mats Jönsson, Karin Annersten, Frida Rosengren, Karin Jirström, Jaroslaw Kosieradzki, Lars Ek, Åke Borg, Maria Planck, Göran Jönsson, Johan Staaf
Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients)...
March 16, 2017: Oncotarget
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