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Stratified medicine in cancer

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https://www.readbyqxmd.com/read/29896316/premenopausal-breast-cancer-potential-clinical-utility-of-a-multi-omics-based-machine-learning-approach-for-patient-stratification
#1
Holger Fröhlich, Sabyasachi Patjoshi, Kristina Yeghiazaryan, Christina Kehrer, Walther Kuhn, Olga Golubnitschaja
Background: The breast cancer (BC) epidemic is a multifactorial disease attributed to the early twenty-first century: about two million of new cases and half a million deaths are registered annually worldwide. New trends are emerging now: on the one hand, with respect to the geographical BC prevalence and, on the other hand, with respect to the age distribution. Recent statistics demonstrate that young populations are getting more and more affected by BC in both Eastern and Western countries...
June 2018: EPMA Journal
https://www.readbyqxmd.com/read/29807109/affinity-network-fusion-and-semi-supervised-learning-for-cancer-patient-clustering
#2
Tianle Ma, Aidong Zhang
Defining subtypes of complex diseases such as cancer and stratifying patient groups with the same disease but different subtypes for targeted treatments is important for personalized and precision medicine. Approaches that incorporate multi-omic data are more advantageous to those using only one data type for patient clustering and disease subtype discovery. However, it is challenging to integrate multi-omic data as they are heterogeneous and noisy. In this paper, we present Affinity Network Fusion (ANF) to integrate multi-omic data for patient clustering...
May 25, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29782246/precision-medicine-and-radiogenomics-in-breast-cancer-new-approaches-toward-diagnosis-and-treatment
#3
Katja Pinker, Joanne Chin, Amy N Melsaether, Elizabeth A Morris, Linda Moy
Precision medicine is medicine optimized to the genotypic and phenotypic characteristics of an individual and, when present, his or her disease. It has a host of targets, including genes and their transcripts, proteins, and metabolites. Studying precision medicine involves a systems biology approach that integrates mathematical modeling and biology genomics, transcriptomics, proteomics, and metabolomics. Moreover, precision medicine must consider not only the relatively static genetic codes of individuals, but also the dynamic and heterogeneous genetic codes of cancers...
June 2018: Radiology
https://www.readbyqxmd.com/read/29779563/association-of-polygenic-risk-scores-for-multiple-cancers-in-a-phenome-wide-study-results-from-the-michigan-genomics-initiative
#4
Lars G Fritsche, Stephen B Gruber, Zhenke Wu, Ellen M Schmidt, Matthew Zawistowski, Stephanie E Moser, Victoria M Blanc, Chad M Brummett, Sachin Kheterpal, Gonçalo R Abecasis, Bhramar Mukherjee
Health systems are stewards of patient electronic health record (EHR) data with extraordinarily rich depth and breadth, reflecting thousands of diagnoses and exposures. Measures of genomic variation integrated with EHRs offer a potential strategy to accurately stratify patients for risk profiling and discover new relationships between diagnoses and genomes. The objective of this study was to evaluate whether polygenic risk scores (PRS) for common cancers are associated with multiple phenotypes in a phenome-wide association study (PheWAS) conducted in 28,260 unrelated, genotyped patients of recent European ancestry who consented to participate in the Michigan Genomics Initiative, a longitudinal biorepository effort within Michigan Medicine...
May 17, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29764892/intense-exercise-for-survival-among-men-with-metastatic-castrate-resistant-prostate-cancer-interval-gap4-a-multicentre-randomised-controlled-phase-iii-study-protocol
#5
Robert U Newton, Stacey A Kenfield, Nicolas H Hart, June M Chan, Kerry S Courneya, James Catto, Stephen P Finn, Rosemary Greenwood, Daniel C Hughes, Lorelei Mucci, Stephen R Plymate, Stephan F E Praet, Emer M Guinan, Erin L Van Blarigan, Orla Casey, Mark Buzza, Sam Gledhill, Li Zhang, Daniel A Galvão, Charles J Ryan, Fred Saad
INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC)...
May 14, 2018: BMJ Open
https://www.readbyqxmd.com/read/29758342/next-generation-sequencing-in-drug-development-target-identification-and-genetically-stratified-clinical-trials
#6
REVIEW
Abolfazl Doostparast Torshizi, Kai Wang
Next-generation sequencing (NGS) enabled high-throughput analysis of genotype-phenotype relationships on human populations, ushering in a new era of genetics-informed drug development. The year 2017 was remarkable, with the first FDA-approved gene therapy for cancer (Kymriah™) and for inherited diseases (LUXTURNA™), the first multiplex NGS panel for companion diagnostics (MSK-IMPACT™) and the first drug targeting a genetic signature rather than a disease (Keytruda® ). We envision that population-scale NGS with paired electronic health records (EHRs) will become a routine measure in the drug development process for the identification of novel drug targets, and that genetically stratified clinical trials could be widely adopted to improve power in precision-medicine-guided drug development...
May 24, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29737630/a-framework-for-identifying-treatment-covariate-interactions-in-individual-participant-data-network-meta-analysis
#7
S C Freeman, D Fisher, J F Tierney, J R Carpenter
BACKGROUND: Stratified medicine seeks to identify patients most likely to respond to treatment. Individual participant data (IPD) network meta-analysis (NMA) models have greater power than individual trials to identify treatment-covariate interactions (TCI). TCI contain "within" and "across" trial interactions, where the across trial interaction is more susceptible to confounding and ecological bias. METHODS: We considered a network of IPD from 37 trials (5922 patients) for cervical cancer (2394 events), where previous research identified disease stage as a potential interaction covariate...
May 8, 2018: Research Synthesis Methods
https://www.readbyqxmd.com/read/29713984/biomarkers-of-barrett-s-esophagus-from-the-laboratory-to-clinical-practice
#8
REVIEW
Vani J A Konda, Rhonda F Souza
The currently recommended approach to managing cancer risk for patients with Barrett's esophagus is endoscopic surveillance including a biopsy protocol to sample the esophageal tissue randomly to detect dysplasia. However, there are numerous limitations in this practice that rely on the histopathological grading of dysplasia alone to make clinical decisions. The availability of in silico models demonstrating the potential cost-effectiveness of biomarker-based stratification has increased interest in finding a clinically relevant "Barrett's biomarker...
April 30, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29713660/esophageal-3d-culture-systems-as-modeling-tools-in-esophageal-epithelial-pathobiology-and-personalized-medicine
#9
REVIEW
Kelly A Whelan, Amanda B Muir, Hiroshi Nakagawa
The stratified squamous epithelium of the esophagus shows a proliferative basal layer of keratinocytes that undergo terminal differentiation in overlying suprabasal layers. Esophageal pathologies, including eosinophilic esophagitis, gastroesophageal reflux disease, Barrett's esophagus, squamous cell carcinoma, and adenocarcinoma, cause perturbations in the esophageal epithelial proliferation-differentiation gradient. Three-dimensional (3D) culture platforms mimicking in vivo esophageal epithelial tissue architecture ex vivo have emerged as powerful experimental tools for the investigation of esophageal biology in the context of homeostasis and pathology...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29668600/chilean-gastric-cancer-task-force-a-study-protocol-to-obtain-a-clinical-and-molecular-classification-of-a-cohort-of-gastric-cancer-patients
#10
Gareth I Owen, Mauricio P Pinto, Ignacio N Retamal, María F Fernádez, Betzabe Cisternas, Sebastian Mondaca, Cesar Sanchez, Hector Galindo, Bruno Nervi, Carolina Ibañez, Francisco Acevedo, Jorge Madrid, José Peña, Maria Loreto Bravo, Maria Jose Maturana, Miguel Cordova-Delgado, Diego Romero, Nathaly de la Jara, Javiera Torres, Maria Rodriguez-Fernandez, Manuel Espinoza, Carlos Balmaceda, Matías Freire, Valentina Gárate-Calderón, Fernando Crovari, Paula Jimenez-Fonseca, Alberto Carmona-Bayonas, Ariel Zwenger, Ricardo Armisen, Alejandro H Corvalan, Marcelo Garrido
Gastric cancer (GC) is the world's second-leading cause of neoplastic mortality. Genetic alterations, response to treatments, and mortality rates are highly heterogeneous across different regions. Within Latin America, GC is the leading cause of cancer death in Chile, affecting 17.6 per 100,000 people and causing >3000 deaths/y. Clinical outcomes and response to "one size fits all" therapies are highly heterogeneous and thus a better stratification of patients may aid cancer treatment and response...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29658620/impact-of-economic-sanctions-on-access-to-noncommunicable-diseases-medicines-in-the-islamic-republic-of-iran
#11
Mehrnaz Kheirandish, Vida Varahrami, Abbas Kebriaeezade, Abdol Majid Cheraghali
Background: It has been argued that economic sanctions and the economic crisis have adversely affected access to drugs. Aim: To assess the impact of economic sanctions on the Iranian banking system in 2011 and Central Bank in 2012 on access to and use of drugs for noncommunicable diseases (NCDs). Methods: An interrupted time series study assessed the effects of sanctions on drugs for diabetes (5 drug groups), asthma (5 drug groups), cancer (14 drugs) and multiple sclerosis (2 drugs)...
April 5, 2018: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
https://www.readbyqxmd.com/read/29610289/e-cadherin-ros1-inhibitor-synthetic-lethality-in-breast-cancer
#12
Ilirjana Bajrami, Rebecca Marlow, Marieke van de Ven, Rachel Brough, Helen N Pemberton, Jessica Frankum, Feifei Song, Rumana Rafiq, Asha Konde, Dragomir B Krastev, Malini Menon, James Campbell, Aditi Gulati, Rahul Kumar, Stephen J Pettitt, Mark D Gurden, Marta Llorca Cardenosa, Irene Chong, Patrycja Gazinska, Fredrik Wallberg, Elinor J Sawyer, Lesley-Ann Martin, Mitch Dowsett, Spiros Linardopoulos, Rachael Natrajan, Colm J Ryan, Patrick W B Derksen, Jos Jonkers, Andrew N J Tutt, Alan Ashworth, Christopher J Lord
The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between E-cadherin deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib...
April 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29530834/radical-hysterectomy-and-age-outcomes-comparison-based-on-a-minimally-invasive-vs-an-open-approach
#13
Ricardo Dos Reis, Carlos E M C Andrade, Michael Frumovitz, Mark Munsell, Pedro T Ramirez
STUDY OBJECTIVE: To compare outcomes of radical hysterectomy (RH) across age groups based on surgical approach: minimally invasive surgery (MIS) vs laparotomy (LP). DESIGN: Cross-sectional retrospective review (Canadian Task Force classification II-2). SETTING: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center. PATIENTS: Patients with early-stage cervical cancer who underwent RH at a tertiary cancer center between 1990 and 2013...
March 9, 2018: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/29443392/spatial-aspects-of-oncogenic-signalling-determine-the-response-to-combination-therapy-in-slice-explants-from-kras-driven-lung-tumours
#14
Katja Närhi, Ashwini S Nagaraj, Elina Parri, Riku Turkki, Petra W van Duijn, Annabrita Hemmes, Jenni Lahtela, Virva Uotinen, Mikko I Mäyränpää, Kaisa Salmenkivi, Jari Räsänen, Nina Linder, Jan Trapman, Antti Rannikko, Olli Kallioniemi, Taija M Af Hällström, Johan Lundin, Wolfgang Sommergruber, Simon Anders, Emmy W Verschuren
A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision-cut slices from Kras-driven non-small-cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen-activated protein kinase (MAPK) activity in adenocarcinoma...
May 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29405335/dielectrophoretic-analysis-of-treated-cancer-cells-for-rapid-assessment-of-treatment-efficacy
#15
Sina Mahabadi, Fatima H Labeed, Michael P Hughes
Whilst personalized medicine (where interventions are precisely tailored to a patient's genotype and phenotype, as well as the nature and state of the disease) is regarded as an optimal form of treatment, the time and cost associated with it means it remains inaccessible to the greater public. A simpler alternative, stratified medicine, identifies groups of patients who are likely to respond to a given treatment. This allows appropriate treatments to be selected at the start of therapy, avoiding the common "trial and error" approach of replacing a therapy only once it is demonstrated to be ineffective in the patient...
April 2018: Electrophoresis
https://www.readbyqxmd.com/read/29362299/-risk-assessment-of-hematologic-malignancy-treatment-of-the-elderly
#16
Hidenori Sasaki, Yasushi Takamatsu
Along with the aging society in Japan, the number ofelderly cancer patients is increasing, and hematological malignancy is no exception. Treatment ofhematological malignancy is mainly chemotherapy and furthermore it is necessary to keep its dose intensity. In the elderly, adverse events may be strong due to deterioration oforgan function, comorbidity, etc., and it is difficult for individual differences to decide chemotherapy regimen and dose. Geriatric assessment(GA)used in the field of geriatric medicine is reported to be useful for risk assessment of chemotherapy...
January 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29341479/nuclear-division-cycle-80-promotes-malignant-progression-and-predicts-clinical-outcome-in-colorectal-cancer
#17
Xuebing Yan, Linsheng Huang, Liguo Liu, Huanlong Qin, Zhenshun Song
Colorectal cancer (CRC) is a common human malignancy worldwide and increasing studies have attributed its malignant progression to abnormal molecular changes in cancer cells. Nuclear division cycle 80 (NDC80) is a newly discovered oncoprotein that regulates cell proliferation and cycle in numerous malignancies. However, its clinical significance and biological role in CRC remain unclear. Therefore, in this study, we firstly analyze its expression in a retrospective cohort enrolling 224 CRC patients and find its overexpression is significantly correlated with advanced tumor stage and poor prognosis in CRC patients...
February 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29322559/cest-dixon-for-human-breast-lesion-characterization-at-3-t-a-preliminary-study
#18
Shu Zhang, Stephen Seiler, Xinzeng Wang, Ananth J Madhuranthakam, Jochen Keupp, Emily E Knippa, Robert E Lenkinski, Elena Vinogradov
PURPOSE: Chemical exchange saturation transfer (CEST) MRI for breast lesion characterization is promising. However, artifacts are prone to develop in breast CEST imaging as a result of strong lipid signals. The aims of the study are (i) to develop and validate the CEST-Dixon imaging sequence for simultaneous water-fat separation and B0 mapping; and (ii) use the CEST-Dixon method to characterize suspicious lesions in patients undergoing percutaneous biopsy. METHODS: The gradient-echo multi-echo Dixon acquisition is used to create fat-free CEST and B0 maps...
January 10, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29259702/epithelial-stem-cell-culture-modeling-human-disease-and-applications-for-regenerative-medicine
#19
REVIEW
Yusuke Yamamoto, Takahiro Ochiya
The inability to maintain the immaturity of stem cell populations in vitro restricts the long-term expansion of various types of human epithelial stem cells. However, recent technical advances in epithelial stem cell culture have led to the development of novel in vitro strategies for regenerating epithelial tissues and for closely mimicking human diseases such as cancer and inflammation. Specifically, improvements in culture conditions provided by small molecules in combination with three-dimensional (3D) culture approaches have facilitated the establishment of in vitro systems that recapitulate biological properties in epithelial organs, and these systems may be used to model disease...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29246028/challenges-and-future-of-biomarker-tests-in-the-era-of-precision-oncology-can-we-rely-on-immunohistochemistry-ihc-or-fluorescence-in-situ-hybridization-fish-to-select-the-optimal-patients-for-matched-therapy
#20
REVIEW
Young Kwang Chae, Ayush Arya, Lauren Chiec, Hiral Shah, Ari Rosenberg, Sandip Patel, Kirtee Raparia, Jaehyuk Choi, Derek A Wainwright, Victoria Villaflor, Massimo Cristofanilli, Francis Giles
Molecular techniques have improved our understanding of the pathogenesis of cancer development. These techniques have also fueled the rational development of targeted drugs for patient populations stratified by their genetic characteristics. These novel methods have changed the classic paradigm of diagnostic pathology; among them are IHC, FISH, polymerase chain reaction (PCR) and microarray technology. IHC and FISH detection methods for human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR) and programmed death ligand-1 (PD-L1) were recently approved by the Food and Drug Administration (FDA) as routine clinical practice for cancer patients...
November 21, 2017: Oncotarget
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