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Cancer precision medicine

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https://www.readbyqxmd.com/read/29028368/a-window-into-clinical-next-generation-sequencing-based-oncology-testing-practices
#1
Rakesh Nagarajan, Angela N Bartley, Julia A Bridge, Lawrence J Jennings, Suzanne Kamel-Reid, Annette Kim, Alexander J Lazar, Neal I Lindeman, Joel Moncur, Alex J Rai, Mark J Routbort, Patricia Vasalos, Jason D Merker
CONTEXT: - Detection of acquired variants in cancer is a paradigm of precision medicine, yet little has been reported about clinical laboratory practices across a broad range of laboratories. OBJECTIVE: - To use College of American Pathologists proficiency testing survey results to report on the results from surveys on next-generation sequencing-based oncology testing practices. DESIGN: - College of American Pathologists proficiency testing survey results from more than 250 laboratories currently performing molecular oncology testing were used to determine laboratory trends in next-generation sequencing-based oncology testing...
October 13, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29026940/advanced-bioanalytics-for-precision-medicine
#2
Aldo Roda, Elisa Michelini, Cristiana Caliceti, Massimo Guardigli, Mara Mirasoli, Patrizia Simoni
Precision medicine is a new paradigm that combines diagnostic, imaging, and analytical tools to produce accurate diagnoses and therapeutic interventions tailored to the individual patient. This approach stands in contrast to the traditional "one size fits all" concept, according to which researchers develop disease treatments and preventions for an "average" patient without considering individual differences. The "one size fits all" concept has led to many ineffective or inappropriate treatments, especially for pathologies such as Alzheimer's disease and cancer...
October 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29025326/onco-proteogenomics-multi-omics-level-data-integration-for-accurate-phenotype-prediction
#3
Lampros Dimitrakopoulos, Ioannis Prassas, Eleftherios P Diamandis, George S Charames
The overall goal of translational oncology is to identify molecular alterations indicative of cancer or of responsiveness to specific therapeutic regimens. While next-generation sequencing has played a pioneering role in this quest, the latest advances in proteomic technologies promise to provide a holistic approach to the further elucidation of tumor biology. Genetic information may be written in DNA and flow from DNA to RNA to protein, according to the central dogma of molecular biology, but the observed phenotype is dictated predominantly by the DNA protein coding region-derived proteotype...
October 12, 2017: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/29024958/a-computable-pathology-report-for-precision-medicine-extending-an-observables-ontology-unifying-snomed-ct-and-loinc
#4
Walter S Campbell, Daniel Karlsson, Daniel J Vreeman, Audrey J Lazenby, Geoffrey A Talmon, James R Campbell
Background: The College of American Pathologists (CAP) introduced the first cancer synoptic reporting protocols in 1998. However, the objective of a fully computable and machine-readable cancer synoptic report remains elusive due to insufficient definitional content in Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes (LOINC). To address this terminology gap, investigators at the University of Nebraska Medical Center (UNMC) are developing, authoring, and testing a SNOMED CT observable ontology to represent the data elements identified by the synoptic worksheets of CAP...
September 13, 2017: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/29024838/organ-on-chip-models-of-cancer-metastasis-for-future-personalized-medicine-from-chip-to-the-patient
#5
REVIEW
D Caballero, S Kaushik, V M Correlo, J M Oliveira, R L Reis, S C Kundu
Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease...
October 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/29023443/systematic-network-based-characterization-of-therapeutic-target-inhibitors
#6
Yao Shen, Mariano J Alvarez, Brygida Bisikirska, Alexander Lachmann, Ronald Realubit, Sergey Pampou, Jorida Coku, Charles Karan, Andrea Califano
A large fraction of the proteins that are being identified as key tumor dependencies represent poor pharmacological targets or lack clinically-relevant small-molecule inhibitors. Availability of fully generalizable approaches for the systematic and efficient prioritization of tumor-context specific protein activity inhibitors would thus have significant translational value. Unfortunately, inhibitor effects on protein activity cannot be directly measured in systematic and proteome-wide fashion by conventional biochemical assays...
October 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29022089/quantification-of-altered-tissue-turnover-in-a-liquid-biopsy-a-proposed-precision-medicine-tool-to-assess-chronic-inflammation-and-desmoplasia-associated-with-a-pro-cancerous-niche-and-response-to-immuno-therapeutic-anti-tumor-modalities
#7
REVIEW
Nicholas Willumsen, Louise B Thomsen, Cecilie L Bager, Christina Jensen, Morten A Karsdal
Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a need for novel biomarkers that can predict and monitor treatment. Tumor microenvironment alterations, more specifically the state of chronic inflammation and desmoplasia (tumor fibrosis), are important factors to consider in this context...
October 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29020110/comprehensive-benchmarking-of-snv-callers-for-highly-admixed-tumor-data
#8
Regina Bohnert, Sonia Vivas, Gunther Jansen
Precision medicine attempts to individualize cancer therapy by matching tumor-specific genetic changes with effective targeted therapies. A crucial first step in this process is the reliable identification of cancer-relevant variants, which is considerably complicated by the impurity and heterogeneity of clinical tumor samples. We compared the impact of admixture of non-cancerous cells and low somatic allele frequencies on the sensitivity and precision of 19 state-of-the-art SNV callers. We studied both whole exome and targeted gene panel data and up to 13 distinct parameter configurations for each tool...
2017: PloS One
https://www.readbyqxmd.com/read/29019032/nanotechnology-as-a-delivery-tool-for-precision-cancer-therapies
#9
Bhawna Sharma, Rachael M Crist, Pavan P Adiseshaiah
Genomic analyses from patients with cancer have improved the understanding of the genetic elements that drive the disease, provided new targets for treating this relentless disease, and offered criteria for stratifying patient populations that will benefit most from treatments. In the last decade, several new targeted therapies have been approved by the FDA based on these omics findings, leading to significantly improved survival and quality of life for select patient populations. However, many of these precision medicines, e...
October 10, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28993799/genetic-characterization-of-brain-metastases-in-the-era-of-targeted-therapy
#10
REVIEW
Catherine H Han, Priscilla K Brastianos
In the current era of molecularly targeted therapies and precision medicine, choice of cancer treatment has been increasingly tailored according to the molecular or genomic characterization of the cancer the individual has. Previously, the clinical observation of inadequate control of brain metastases was widely attributed to a lack of central nervous system (CNS) penetration of the anticancer drugs. However, more recent data have suggested that there are genetic explanations for such observations. Genomic analyses of brain metastases and matching primary tumor and other extracranial metastases have revealed that brain metastases can harbor potentially actionable driver mutations that are unique to them...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28989987/towards-a-better-cancer-precision-medicine-systems-biology-meets-immunotherapy
#11
Bhavneet Bhinder, Olivier Elemento
Systems biology approaches that embrace the complexity of cancer are starting to gain traction in the development of new anticancer therapeutic strategies. In this review we describe how genomic analyses are helping improve our understanding of response to immunotherapy, a front-runner in cancer treatment. We argue that systems-level approaches are needed to help understand the concerted impact of tumor-specific and immune-specific molecular features on clinical outcomes, predict responders and unravel the complexity of tumor ecosystems...
April 2017: Current opinion in systems biology
https://www.readbyqxmd.com/read/28989095/risk-factors-and-prevention-of-hepatocellular-carcinoma-in-the-era-of-precision-medicine
#12
REVIEW
Naoto Fujiwara, Scott L Friedman, Nicolas Goossens, Yujin Hoshida
Chronic fibrotic liver disease caused by viral or metabolic etiologies is a high-risk condition for developing hepatocellular carcinoma (HCC). Even after complete HCC tumor resection or ablation, the carcinogenic tissue microenvironment in the remnant liver can give rise to recurrent de novo HCC tumors, which progress into incurable, advanced-stage disease in the majority of patients. Thus, early detection and prevention of HCC development is, in principle, the most impactful strategy to improve patient prognosis...
October 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28984192/a-link-prediction-approach-to-cancer-drug-sensitivity-prediction
#13
Turki Turki, Zhi Wei
BACKGROUND: Predicting the response to a drug for cancer disease patients based on genomic information is an important problem in modern clinical oncology. This problem occurs in part because many available drug sensitivity prediction algorithms do not consider better quality cancer cell lines and the adoption of new feature representations; both lead to the accurate prediction of drug responses. By predicting accurate drug responses to cancer, oncologists gain a more complete understanding of the effective treatments for each patient, which is a core goal in precision medicine...
October 3, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28983483/a-comprehensive-infrastructure-for-big-data-in-cancer-research-accelerating-cancer-research-and-precision-medicine
#14
Izumi V Hinkson, Tanja M Davidsen, Juli D Klemm, Anthony R Kerlavage, Warren A Kibbe
Advancements in next-generation sequencing and other -omics technologies are accelerating the detailed molecular characterization of individual patient tumors, and driving the evolution of precision medicine. Cancer is no longer considered a single disease, but rather, a diverse array of diseases wherein each patient has a unique collection of germline variants and somatic mutations. Molecular profiling of patient-derived samples has led to a data explosion that could help us understand the contributions of environment and germline to risk, therapeutic response, and outcome...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28982744/egfr-mutant-non-small-cell-lung-cancer-in-the-era-of-precision-medicine-importance-of-germline-egfr-t790m-testing
#15
Ammar Sukari, Misako Nagasaka, Erin Wakeling
With the rapid development of precision medicine, next-generation sequencing (NGS) has provided the ability to uncode tumors at the DNA level. Identifying EGFR mutations and other molecular changes has become more crucial in the management of non-small cell lung cancer (NSCLC) than ever before. Although the histologic subtypes in patients with advanced NSCLC remain valid in determining treatment options, the detection of specific molecular signatures such as de novo T790M with sensitizing EGFR mutations could be more useful than the histologic subtype itself...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28982488/twenty-first-century-precision-medicine-in-oncology-genomic-profiling-in-patients-with-cancer
#16
REVIEW
Mitesh J Borad, Patricia M LoRusso
The advent of next-generation sequencing has accelerated the implementation of genomic profiling in the care and management of patients with cancer. Initial efforts have focused on target identification in patients with advanced cancer. Prognostication, resistance detection, disease monitoring, and early detection efforts are also underway. This review highlights some of the challenges in this evolving space. This includes choosing between gene-panel and comprehensive approaches, DNA and transcriptome data integration, reduction of false-positive variants, addressing tumor heterogeneity, establishment of workflows to address unsolicited findings, and data sharing and privacy concerns...
October 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28981626/mathematical-modeling-and-computational-prediction-of-cancer-drug-resistance
#17
Xiaoqiang Sun, Bin Hu
Diverse forms of resistance to anticancer drugs can lead to the failure of chemotherapy. Drug resistance is one of the most intractable issues for successfully treating cancer in current clinical practice. Effective clinical approaches that could counter drug resistance by restoring the sensitivity of tumors to the targeted agents are urgently needed. As numerous experimental results on resistance mechanisms have been obtained and a mass of high-throughput data has been accumulated, mathematical modeling and computational predictions using systematic and quantitative approaches have become increasingly important, as they can potentially provide deeper insights into resistance mechanisms, generate novel hypotheses or suggest promising treatment strategies for future testing...
June 23, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28980455/clinical-proteomics-for-precision-medicine-the-bladder-cancer-case
#18
REVIEW
Agnieszka Latosinska, Maria Frantzi, Antonia Vlahou, Axel S Merseburger, Harald Mischak
Precision medicine can improve patient management by guiding therapeutic decision based on molecular characteristics. The concept has been extensively addressed through the application of -omics based approaches. Proteomics attract high interest, as proteins reflect a "real-time" dynamic molecular phenotype. Focusing on proteomics applications for personalized medicine, a literature search was conducted to cover: a) disease prevention, b) monitoring/ prediction of treatment response, c) stratification to guide intervention and d) identification of drug targets...
October 5, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28977985/improving-radiotherapy-in-cancer-treatment-promises-and-challenges
#19
REVIEW
Helen H W Chen, Macus Tien Kuo
Effective radiotherapy for cancer has relied on the promise of maximally eradicating tumor cells while minimally killing normal cells. Technological advancement has provided state-of-the-art instrumentation that enables delivery of radiotherapy with great precision to tumor lesions with substantial reduced injury to normal tissues. Moreover, better understanding of radiobiology, particularly the mechanisms of radiation sensitivity and resistance in tumor lesions and toxicity in normal tissues, has improved the treatment efficacy of radiotherapy...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977847/an-immunocompetent-mouse-model-of-human-glioblastoma
#20
Samantha Semenkow, Shen Li, Ulf D Kahlert, Eric H Raabe, Jiadi Xu, Antje Arnold, Miroslaw Janowski, Byoung Chol Oh, Gerald Brandacher, Jeff W M Bulte, Charles G Eberhart, Piotr Walczak
Orthotopic xenotransplantation studies represent the final stage in preclinical cancer research and could facilitate the implementation of precision medicine. To date, these xenografts have been tested in immunodeficient animals, but complete elimination of the adaptive immunity is a significant drawback. We present a method of efficient human glioblastoma (GBM) cell engraftment in adult mice with intact immune systems, mediated by a transient blockade of T-cell co-stimulation. Compared to transplants grown in immunodeficient hosts, the resulting tumors more accurately resemble the clinical pathophysiology of patient GBMs, which are characterized by blood-brain-barrier leakage and strong neo-vascularization...
September 22, 2017: Oncotarget
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