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Cancer precision medicine

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https://www.readbyqxmd.com/read/29452948/photo-tearable-tape-close-wrapped-upconversion-nanocapsules-for-near-infrared-modulated-efficient-sirna-delivery-and-therapy
#1
Yue Zhang, Kewei Ren, Xiaobo Zhang, Zhicong Chao, Yuqin Yang, Deju Ye, Zhihui Dai, Ying Liu, Huangxian Ju
RNA interference (RNAi) has become an appealing therapeutic approach for cancer and other diseases. One key challenge is the effective protection of these small fragile biomolecules against complicated physiological environments as well as efficient on-demand release. Here we design a photo-tearable polymer tape close-wrapped nanocapsule for efficient NIR modulated siRNA delivery. The photo-tearable nanocapsules comprise core-shell upconversion nanoparticles (UCNPs) coated with mesoporous silica layer for loading of photosensitizer hypocrellin A (HA) and small interfering RNA (siRNA) against polo-like kinase 1 (PLK1), and covalently bound thin membranes of polyethylene glycol (PEG) via a synthesized photocleavable linker (PhL)...
February 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29449090/clinical-and-molecular-characteristics-and-burden-of-kidney-cancer-among-hispanics-and-native-americans-steps-toward-precision-medicine
#2
Ken Batai, Andrew Bergersen, Elinora Price, Kieran Hynes, Nathan A Ellis, Benjamin R Lee
Cancer disparities in Native Americans (NAs) and Hispanic Americans (HAs) vary significantly in terms of cancer incidence and mortality rates across geographic regions. This review reports that kidney and renal pelvis cancers are unevenly affecting HAs and NAs compared to European Americans of non-Hispanic origin, and that currently there is significant need for improved data and reporting to be able to advance toward genomic-based precision medicine for the assessment of such cancers in these medically underserved populations...
February 12, 2018: Clinical Genitourinary Cancer
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/29440675/in-vitro-patient-derived-3d-mesothelioma-tumor-organoids-facilitate-patient-centric-therapeutic-screening
#4
Andrea R Mazzocchi, Shiny A P Rajan, Konstantinos I Votanopoulos, Adam R Hall, Aleksander Skardal
Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29436301/geriatric-assessment-precision-medicine-for-older-adults-with-cancer
#5
Grant R Williams
No abstract text is available yet for this article.
February 2018: Journal of Oncology Practice
https://www.readbyqxmd.com/read/29429018/mobcdb-a-comprehensive-database-integrating-multi-omics-data-on-breast-cancer-for-precision-medicine
#6
Bingbing Xie, Zifeng Yuan, Yadong Yang, Zhidan Sun, Shuigeng Zhou, Xiangdong Fang
BACKGROUND: Breast cancer is one of the most frequently diagnosed cancers among women worldwide, characterized by diverse biological heterogeneity. It is well known that complex and combined gene regulation of multi-omics is involved in the occurrence and development of breast cancer. RESULTS: In this paper, we present the Multi-Omics Breast Cancer Database (MOBCdb), a simple and easily accessible repository that integrates genomic, transcriptomic, epigenomic, clinical, and drug response data of different subtypes of breast cancer...
February 10, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29426058/the-metabolism-of-flubendazole-in-human-liver-and-cancer-cell-lines
#7
Lucie Raisová Stuchlíková, Věra Králová, Kateřina Lněničková, Tomáš Zárybnický, Petra Matoušková, Veronika Hanušová, Martin Ambrož, Zdeněk Šubrt, Lenka Skálová
Flubendazole (FLU), a benzimidazole anthelmintic drug widely used in veterinary medicine, has been approved for the treatment of gut-residing nematodes in humans. In addition, FLU is now considered a promising anticancer agent. Despite this, information about biotransformation of this compound in human is lacking. Moreover, there is no information regarding whether cancer cells are able to metabolize FLU in order to deactivate it. For these reasons, the present study was designed to identify all metabolites of Phase I and Phase II of FLU in human liver and in various cancer cells using UHPLC/MS/MS analysis...
February 9, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29425180/comment-from-the-editor-to-the-special-issue-big-data-and-precision-medicine-series-i-lung-cancer-early-diagnosis
#8
EDITORIAL
Roberto Gasparri, Giulia Sedda, Lorenzo Spaggiari
With this Editorial we want to present the Special Issue "Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis" to the scientific community, which aims to gather experts on the early detection of lung cancer in order to implement common efforts in the fight against cancer.
February 9, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29423054/copy-number-profiles-of-paired-primary-and-metastatic-colorectal-cancers
#9
Futoshi Kawamata, Ann-Marie Patch, Katia Nones, Catherine Bond, Diane McKeone, Sally-Ann Pearson, Shigenori Homma, Cheng Liu, Lochlan Fennell, Troy Dumenil, Gunter Hartel, Nozomi Kobayasi, Hideki Yokoo, Moto Fukai, Hiroshi Nishihara, Toshiya Kamiyama, Matthew E Burge, Christos S Karapetis, Akinobu Taketomi, Barbara Leggett, Nicola Waddell, Vicki Whitehall
Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC). In this study, we compared the copy number profiles of paired primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. Paired primary and metastatic tumors from 16 patients and their adjacent normal tissue samples were analyzed using single nucleotide polymorphism arrays. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 188 genes known to be somatically altered in CRC and 24 genes that are clinically actionable in CRC...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29420101/leveraging-genomics-for-head-and-neck-cancer-treatment
#10
J D Kemmer, D E Johnson, J R Grandis
The genomic landscape of head and neck squamous cell carcinoma (HNSCC) has been recently elucidated. Key epigenetic and genetic characteristics of this cancer have been reported and substantiated in multiple data sets, including those distinctive to the growing subset of human papilloma virus (HPV)-associated tumors. This increased understanding of the molecular underpinnings of HNSCC has not resulted in new approaches to treatment. Three Food and Drug Administration-approved molecular targeting agents are currently available to treat recurrent/metastatic disease, but these have exhibited efficacy only in subsets of HNSCC patients, and thus surgery, chemotherapy, and/or radiation remain as standard approaches...
February 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29419723/development-and-validation-of-a-bioanalytical-method-to-quantitate-enzalutamide-and-its-active-metabolite-n-desmethylenzalutamide-in-human-plasma-application-to-clinical-management-of-metastatic-castration-resistant-prostate-cancer-patients
#11
Guillemette E Benoist, Eric van der Meulen, Inge M van Oort, Jan Hendrik Beumer, Diederik M Somford, Jack A Schalken, David M Burger, Nielka P van Erp
BACKGROUND: Enzalutamide is a potent androgen-signaling receptor inhibitor and is licensed for the treatment of metastatic castration-resistant prostate cancer. N-desmethylenzalutamide is the active metabolite of enzalutamide. A method to quantitate enzalutamide and its active metabolite was developed and validated according to the European Medicine Agency (EMA) guidelines. METHODS: Enzalutamide and N-desmethylenzalutamide were extracted by protein precipitation, separated on a C18 column with gradient elution and analyzed with tandem quadruple mass spectrometry in positive ion mode...
February 5, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29416754/targeted-deep-sequencing-of-circulating-tumor-dna-in-metastatic-pancreatic-cancer
#12
Andreas W Berger, Daniel Schwerdel, Thomas J Ettrich, Alexander Hann, Stefan A Schmidt, Alexander Kleger, Ralf Marienfeld, Thomas Seufferlein
Purpose: Precision medicine in pancreatic ductal adenocarcinoma (PDAC) could be substantially supported by tools that allow to establish and monitor the molecular setup of the tumor. In particular, noninvasive approaches are desirable, but not validated. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Experimental Design: Blood samples from patients with metastatic PDAC prior to and during palliative treatment were collected. ctDNA and corresponding tumor tissue were analyzed by targeted next generation sequencing and droplet digital PCR for the 7 most frequently mutated genes in PDAC (TP53, SMAD4, CDKN2A, KRAS, APC, ATM, and FBXW7)...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416054/evaluation-of-pd-l1-expression-on-vortex-isolated-circulating-tumor-cells-in-metastatic-lung-cancer
#13
Manjima Dhar, Jessica Wong, James Che, Melissa Matsumoto, Tristan Grogan, David Elashoff, Edward B Garon, Jonathan W Goldman, Elodie Sollier Christen, Dino Di Carlo, Rajan P Kulkarni
Metastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses. Important for personalizing therapy, patients with higher intensity staining for PD-L1 on tumor biopsies responded better. Thus, there has been interest in using PD-L1 tumor expression as a criterion for patient selection...
February 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29409135/reassessing-the-value-of-high-volume-cancer-care-in-the-era-of-precision-medicine
#14
Alexander P Cole, Maxine Sun, Stuart R Lipsitz, Akshay Sood, Adam S Kibel, Quoc-Dien Trinh
The ethical and economic discussions regarding the extreme costs of many new cancer therapies are familiar. The authors have long held that changes in cancer care delivery also are an important strategy, yielding large benefits at potentially far lower costs. To put this into context, the authors performed an analysis to compare the overall survival of patients receiving a complex oncologic surgery, radical cystectomy, at high-volume and low-volume centers. Propensity score weighting was performed to simulate random allocation into high-volume versus low-volume centers, as would be the case in a prospective trial...
February 6, 2018: Cancer
https://www.readbyqxmd.com/read/29405770/liquid-biopsy-and-its-role-in-an-advanced-clinical-trial-for-lung-cancer
#15
Donald J Johann, Mathew Steliga, Ik J Shin, Donghoon Yoon, Konstantinos Arnaoutakis, Laura Hutchins, Meeiyueh Liu, Jason Liem, Karl Walker, Andy Pereira, Mary Yang, Susanne K Jeffus, Erich Peterson, Joshua Xu
Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount...
February 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29405335/dielectrophoretic-analysis-of-treated-cancer-cells-for-rapid-assessment-of-treatment-efficacy
#16
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/29395304/management-of-the-toxicities-of-common-targeted-therapeutics-for-gynecologic-cancers
#17
REVIEW
Camille C Gunderson, Ursula Matulonis, Kathleen N Moore
As precision medicine has become a focus in oncology in recent years, many targeted and biologic agents are being used along with or in place of traditional cytotoxic chemotherapy. As these drugs have been developed and some have received FDA approval, we have gained substantial data about the adverse event profiles. However, the management and approach to the toxicities incurred and subsequent complications are often not well understood, especially for physicians who have a varied clinical practice. The purpose of this review is to provide an overview of the frequency and types of adverse events and appropriate management steps when prescribing modern targeted therapies for gynecologic cancers in the classes of anti-angiogenic agents, poly-ADP-ribose polymerase (PARP) inhibitors, and immunotherapy drugs...
January 30, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29395243/risk-prediction-of-cancer-associated-thrombosis-appraising-the-first-decade-and-developing-the-future
#18
Alok A Khorana, Charles W Francis
Cancer-associated venous thromboembolism (VTE) has major consequences for patients, including morbidity and risk of mortality. However, there is substantial variation in risk depending on a multitude of clinical risk factors and many cancer patients are at low risk for VTE. This critical concept of risk variation has led to efforts to identify patients at high or low risk for developing VTE. Our research group and others have focused on understanding and predicting risk of cancer-associated VTE. This narrative review describe research efforts conducted over the past decade, beginning with the 2008 publication of the first validated risk assessment tool in this setting...
January 26, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29394274/xrcc3-thr241met-and-tyms-variable-number-tandem-repeat-polymorphisms-are-associated-with-time-to-metastasis-in-colorectal-cancer
#19
Yanjing He, Michelle E Penney, Amit A Negandhi, Patrick S Parfrey, Sevtap Savas, Yildiz E Yilmaz
BACKGROUND: Metastasis is a major cause of mortality in cancer. Identifying prognostic factors that distinguish patients who will experience metastasis in the short-term and those that will be free of metastasis in the long-term is of particular interest in current medical research. The objective of this study was to examine if select genetic polymorphisms can differentiate colorectal cancer patients based on timing and long-term risk of metastasis. METHODS: The patient cohort consisted of 402 stage I-III colorectal cancer patients with microsatellite instability (MSI)-low (MSI-L) or microsatellite stable (MSS) tumors...
2018: PloS One
https://www.readbyqxmd.com/read/29392535/innovative-methods-for-biomarker-discovery-in-the-evaluation-and-development-of-cancer-precision-therapies
#20
REVIEW
Ijeoma Adaku Umelo, Brunella Costanza, Vincent Castronovo
The discovery of biomarkers able to detect cancer at an early stage, to evaluate its aggressiveness, and to predict the response to therapy remains a major challenge in clinical oncology and precision medicine. In this review, we summarize recent achievements in the discovery and development of cancer biomarkers. We also highlight emerging innovative methods in biomarker discovery and provide insights into the challenges faced in their evaluation and validation.
March 2018: Cancer Metastasis Reviews
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