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Stratified medicine in cancer

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https://www.readbyqxmd.com/read/29610289/e-cadherin-ros1-inhibitor-synthetic-lethality-in-breast-cancer
#1
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-minimally-invasive-vs-open-approach
#2
Ricardo Dos Reis, Carlos E M C Andrade, Michael Frumovitz, Mark Munsell, Pedro T Ramirez
STUDY OBJECTIVE: The goal of our study is to compare outcomes of radical hysterectomy (RH) across age groups based on surgical approach. DESIGN: Cross-sectional study. CANADIAN TASK FORCE CLASSIFICATION: II-2 SETTING: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center. PATIENTS: We retrospectively reviewed patients with early-stage cervical cancer who underwent RH at a tertiary cancer center from 1990 to 2013...
March 9, 2018: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/29443392/spatial-aspects-of-oncogenic-signaling-determine-response-to-combination-therapy-in-slice-explants-from-kras-driven-lung-tumors
#3
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 Af Hällström, Johan Lundin, Wolfgang Sommergruber, Simon Anders, Emmy W Verschuren
A key question in precision medicine is how functional heterogeneity in solid tumors informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signaling and therapy response can be modeled in precision-cut slices from Kras-driven non-small cell lung cancer (NSCLC) of varying histopathologies. Unexpectedly, profiling of in situ tumors demonstrates that signaling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma (ASC), and MAPK activity in adenocarcinoma (AC)...
February 14, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29405335/dielectrophoretic-analysis-of-treated-cancer-cells-for-rapid-assessment-of-treatment-efficacy
#4
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...
February 5, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29362299/-risk-assessment-of-hematologic-malignancy-treatment-of-the-elderly
#5
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
#6
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...
January 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29322559/cest-dixon-for-human-breast-lesion-characterization-at-3-t-a-preliminary-study
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/29245994/clinicopathological-and-prognostic-significance-of-hmga2-overexpression-in-gastric-cancer-a-meta-analysis
#10
Jingyi Zhu, Hailong Wang, Shuangnian Xu, Yingxue Hao
Background: High mobility group protein A2 (HMGA2) overexpression has been reported to be closely related to tumor progression [1-4] and indicate significantly worse overall survival in gastric cancer [5-8]. However, a final consensus regarding this issue has not yet been reached. Thus, we conducted a meta-analysis to evaluate the association between HMGA2 expression and prognosis of gastric cancer patients. Methods: The Cochrane Library, Embase, PubMed, Web of Science and China Biology Medicine databases were searched to identify eligible literature published prior to September 2016...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228059/does-access-to-clinical-study-reports-from-the-european-medicines-agency-reduce-reporting-biases-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials-on-the-effect-of-erythropoiesis-stimulating-agents-in-cancer-patients
#11
REVIEW
Eliane Rohner, Michael Grabik, Thomy Tonia, Peter Jüni, Frank Pétavy, Francesco Pignatti, Julia Bohlius
Since 2010, the European Medicines Agency (EMA) has provided access to clinical study reports (CSRs). We requested CSRs for randomized controlled trials (RCTs) of erythropoiesis-stimulating agents (ESAs) in cancer patients from EMA and identified RCT publications with literature searches. We assessed CSR availability and completeness, the impact of unreported and unpublished data obtained from CSRs on the effects of ESAs on quality of life (QoL) of cancer patients, and discrepancies between data reported in the public domain and in CSRs...
2017: PloS One
https://www.readbyqxmd.com/read/29224672/sle-redefined-on-the-basis-of-molecular-pathways
#12
REVIEW
Guillermo Barturen, Marta E Alarcón-Riquelme
The implementation of precision medicine requires the recruiting of patients in statistically enough numbers, the possibility of obtaining enough materials, and the integration of data from various platforms, which are all real limitations. These types of studies have been performed extensively in cancer but barely on systemic lupus erythematosus (SLE) or other rheumatic diseases. To consider the practical use of the information obtained from such studies, we have to take into account the best biological fluid to use, the ease to perform the analysis in clinical practice, and its relevance to clinical practice...
June 2017: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/29174310/gefitinib-versus-vinorelbine-plus-cisplatin-as-adjuvant-treatment-for-stage-ii-iiia-n1-n2-egfr-mutant-nsclc-adjuvant-ctong1104-a-randomised-open-label-phase-3-study
#13
Wen-Zhao Zhong, Qun Wang, Wei-Min Mao, Song-Tao Xu, Lin Wu, Yi Shen, Yong-Yu Liu, Chun Chen, Ying Cheng, Lin Xu, Jun Wang, Ke Fei, Xiao-Fei Li, Jian Li, Cheng Huang, Zhi-Dong Liu, Shun Xu, Ke-Neng Chen, Shi-Dong Xu, Lun-Xu Liu, Ping Yu, Bu-Hai Wang, Hai-Tao Ma, Hong-Hong Yan, Xue-Ning Yang, Qing Zhou, Yi-Long Wu
BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China...
January 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29170406/an-extracellular-matrix-related-prognostic-and-predictive-indicator-for-early-stage-non-small-cell-lung-cancer
#14
Su Bin Lim, Swee Jin Tan, Wan-Teck Lim, Chwee Teck Lim
The prognosis and prediction of adjuvant chemotherapy (ACT) response in early-stage non-small cell lung cancer (NSCLC) patients remain poor in this era of personalized medicine. We hypothesize that extracellular matrix (ECM)-associated components could be potential markers for better diagnosis and prognosis due to their differential expression in 1,943 primary NSCLC tumors as compared to 303 normal lung tissues. Here we develop a 29-gene ECM-related prognostic and predictive indicator (EPPI). We validate a robust performance of the EPPI risk scoring system in multiple independent data sets, comprising a total of 2,071 early-stage NSCLC tumors...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29154898/evaluation-of-dynamic-contrast-enhanced-mri-biomarkers-for-stratified-cancer-medicine-how-do-permeability-and-perfusion-vary-between-human-tumours
#15
Ross A Little, Hervé Barjat, Jennifer I Hare, Mary Jenner, Yvonne Watson, Susan Cheung, Katherine Holliday, Weijuan Zhang, James P B O'Connor, Simon T Barry, Sanyogitta Puri, Geoffrey J M Parker, John C Waterton
BACKGROUND: Solid tumours exhibit enhanced vessel permeability and fenestrated endothelium to varying degree, but it is unknown how this varies in patients between and within tumour types. Dynamic contrast-enhanced (DCE) MRI provides a measure of perfusion and permeability, the transfer constant Ktrans , which could be employed for such comparisons in patients. AIM: To test the hypothesis that different tumour types exhibit systematically different Ktrans . MATERIALS AND METHODS: DCE-MRI data were retrieved from 342 solid tumours in 230 patients...
February 2018: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/29140483/integrative-whole-person-oncology-care-in-the-uk
#16
Catherine Zollman, Axel Walther, Helen E Seers, Rachel C Jolliffe, Marie J Polley
The term "whole-person cancer care"-an approach that addresses the needs of the person as well as treating the disease-is more widely understood in the United Kingdom than its synonym "integrative oncology." The National Health Service (NHS) provides free access to care for all, which makes it harder to prioritize NHS funding of whole-person medicine, where interventions may be multimodal and lacking in cost-effectiveness data. Despite this, around 30% of cancer patients are known to use some form of complementary or alternative medicine (CAM)...
November 1, 2017: Journal of the National Cancer Institute. Monographs
https://www.readbyqxmd.com/read/29097403/gridss-sensitive-and-specific-genomic-rearrangement-detection-using-positional-de-bruijn-graph-assembly
#17
Daniel L Cameron, Jan Schröder, Jocelyn Sietsma Penington, Hongdo Do, Ramyar Molania, Alexander Dobrovic, Terence P Speed, Anthony T Papenfuss
The identification of genomic rearrangements with high sensitivity and specificity using massively parallel sequencing remains a major challenge, particularly in precision medicine and cancer research. Here, we describe a new method for detecting rearrangements, GRIDSS (Genome Rearrangement IDentification Software Suite). GRIDSS is a multithreaded structural variant (SV) caller that performs efficient genome-wide break-end assembly prior to variant calling using a novel positional de Bruijn graph-based assembler...
December 2017: Genome Research
https://www.readbyqxmd.com/read/29069872/potential-therapeutic-targets-of-triple-negative-breast-cancer-based-on-its-intrinsic-subtype
#18
REVIEW
Fangyuan Shao, Heng Sun, Chu-Xia Deng
Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer, which is characterized as estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative. TNBC is the most difficult breast cancer subgroup to treat, due to its unresponsiveness to current clinical targeted therapies, high rate of recurrence, and poor prognosis. Thus, there is an urgent medical need to identify therapeutic targets and develop more effective stratified medicine for the treatment of TNBC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29068364/advances-in-precision-medicine-tailoring-individualized-therapies
#19
Kyle B Matchett, Niamh Lynam-Lennon, R William Watson, James A L Brown
The traditional bench-to-bedside pipeline involves using model systems and patient samples to provide insights into pathways deregulated in cancer. This discovery reveals new biomarkers and therapeutic targets, ultimately stratifying patients and informing cohort-based treatment options. Precision medicine (molecular profiling of individual tumors combined with established clinical-pathological parameters) reveals, in real-time, individual patient's diagnostic and prognostic risk profile, informing tailored and tumor-specific treatment plans...
October 25, 2017: Cancers
https://www.readbyqxmd.com/read/29063873/future-role-of-endoscopic-ultrasound-in-personalized-management-of-pancreatic-cancer
#20
REVIEW
Marie Ooi, An Phan, Nam Q Nguyen
Pancreatic ductal adenocarcinoma (PDAC) is aggressive and lethal with the majority of cases presenting with advanced unresectable disease due to delayed diagnosis. Despite improvement in surgery, chemotherapies, and intensive care medicine, the outcome of PDAC remains poor, which may relate to the tumor biology. Recent data suggest that PDAC is a "systemic cancer" with complex molecular or genomics derangement with marked heterogeneity. The ability to characterize the PDAC better by detailed evaluation of tissue biomarkers or genomics allows for improved prediction of prognosis and stratification of treatment, a concept known as "personalized cancer therapy...
September 2017: Endoscopic Ultrasound
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