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Cancer precision medicine

Hend M Dawood, Reham S Ibrahim, Eman Shawky, Hala M A Hammoda, Aly M Metwally
ETHNOPHARMACOLOGICAL RELEVANCE: Aromatase enzyme (CYP19) is widely known as a critical target protein for treating hormone-dependent breast cancer. Natural products from traditional medicinal plants continue to be an active source of aromatase inhibitors. Meanwhile, high cost of experimental work and low hit rate associated with HTS have stimulated the implementation of in-silico virtual screening to resolve these pitfalls, where coupling of both classical wet lab procedure and VS may offer a more deepened access to bioactive compounds with less work and time waste...
June 14, 2018: Journal of Ethnopharmacology
Kivilcim Ozturk, Michelle Dow, Daniel E Carlin, Rafael Bejar, Hannah Carter
Precision cancer medicine promises to tailor clinical decisions to patients using genomic information. Indeed, successes of drugs targeting genetic alterations in tumors, such as imatinib that targets BCR-ABL in chronic myelogenous leukemia, have demonstrated the power of this approach. However biological systems are complex, and patients may differ not only by the specific genetic alterations in their tumor, but by more subtle interactions among such alterations. Systems biology and more specifically, network analysis, provides a framework for advancing precision medicine beyond clinical actionability of individual mutations...
June 14, 2018: Journal of Molecular Biology
Xi Zhong, Zhexu Guo, Peng Gao, Yongxi Song, Jingxu Sun, Xiaowan Chen, Yu Sun, Zhenning Wang
BACKGROUND: Most race/ethnicity-oriented investigations focus on Caucasian Americans (whites) and African Americans (blacks), leaving Asians, Hispanic white (Hispanics), and other minorities less well studied. Adjuvant chemotherapy (CT) after curative resection is critical to patients with locally advanced colon cancer (LACC). We studied the racial disparities in the adjuvant CT of LACC to aid in selecting optimal treatments for people from different races/ethnicities in this era of precision medicine...
August 2018: Journal of Surgical Research
Qin Xiao, Lianzhou Chen, Haiqing Luo, Hongmei Li, Qingming Kong, Fei Jiao, Shifeng Pang, Ming Zhang, Feifei Lan, Wenguo Fan, Hui Luo, Tao Tao, Xiao Zhu
BACKGROUND: CHD5 is a conventional tumour-suppressing gene in many tumours. The aim of this study was to determine whether CHD5 variants contribute to the risk of hepatocellular carcinoma (HCC). METHODS: Gene variants were identified using next-generation sequencing targeted on referenced mutations followed by TaqMan genotyping in two case-control studies. RESULTS: We discovered a rare variant (haplotype AG) in CHD5 (rs12564469-rs9434711) that was markedly associated with the risk of HCC in a Chinese population...
June 15, 2018: BMC Cancer
Kathrin Scheckenbach
Precision medicine is increasingly pushed forward, also with respect to upcoming new targeted therapies. Individual characterization of diseases on the basis of biomarkers is a prerequisite for this development. So far, biomarkers are characterized clinically, histologically or on a molecular level. The implementation of broad screening methods ("Omics") and the analysis of big data - in addition to single markers - allow to define biomarker signatures. Next to "Genomics", "Proteomics", and "Metabolicis", "Radiomics" gained increasing interest during the last years...
March 2018: Laryngo- Rhino- Otologie
Andrew J Aguirre, Jonathan A Nowak, Nicholas D Camarda, Richard A Moffitt, Arezou A Ghazani, Mehlika Hazar-Rethinam, Srivatsan Raghavan, Jaegil Kim, Lauren K Brais, Dorisanne Ragon, Marisa W Welch, Emma Reilly, Devin McCabe, Lori Marini, Kristin Anderka, Karla Helvie, Nelly Oliver, Ana Babic, Annacarolina Da Silva, Brandon Nadres, Emily E Van Seventer, Heather A Shahzade, Joseph P St Pierre, Kelly P Burke, Thomas E Clancy, James M Cleary, Leona A Doyle, Kunal Jajoo, Nadine J McCleary, Jeffrey A Meyerhardt, Janet E Murphy, Kimmie Ng, Anuj K Patel, Kimberly Perez, Michael H Rosenthal, Douglas A Rubinson, Marvin Ryou, Geoffrey I Shapiro, Ewa Sicinska, Stuart G Silverman, Rebecca J Nagy, Richard B Lanman, Deborah Knoerzer, Dean J Welsch, Matthew B Yurgelun, Charles S Fuchs, Levi A Garraway, Gad Getz, Jason L Hornick, Bruce E Johnson, Matthew H Kulke, Robert J Mayer, Jeffrey W Miller, Paul B Shyn, David A Tuveson, Nikhil Wagle, Jen Jen Yeh, William C Hahn, Ryan B Corcoran, Scott L Carter, Brian M Wolpin
Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole exome sequencing and RNA-sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data...
June 14, 2018: Cancer Discovery
Alexandra S Whale, Gerwyn M Jones, Jernej Pavšič, Tanja Dreo, Nicholas Redshaw, Sema Akyurek, Muslum Akgoz, Carla Divieto, Maria PaolaSassi, Hua-Jun He, Kenneth D Cole, Young-Kyung Bae, Sang-Ryoul Park, Liesbet Deprez, Philippe Corbisier, Sonia Garrigou, Valérie Taly, Raquel Larios, Simon Cowen, Denise M O'Sullivan, Claire A Bushell, Heidi Goenaga-Infante, Carole A Foy, Alison J Woolford, Helen Parkes, Jim F Huggett, Alison S Devonshire
BACKGROUND: Genetic testing of tumor tissue and circulating cell-free DNA for somatic variants guides patient treatment of many cancers. Such measurements will be fundamental in the future support of precision medicine. However, there are currently no primary reference measurement procedures available for nucleic acid quantification that would support translation of tests for circulating tumor DNA into routine use. METHODS: We assessed the accuracy of digital PCR (dPCR) for copy number quantification of a frequently occurring single-nucleotide variant in colorectal cancer ( KRAS c...
June 14, 2018: Clinical Chemistry
Naohiko Yoshizawa, Reiko Yamada, Takashi Sakuno, Hiroyuki Inoue, Hiroshi Miura, Toshifumi Takeuchi, Misaki Nakamura, Yasuhiko Hamada, Masaki Katsurahara, Kyosuke Tanaka, Noriyuki Horiki, Yoshiyuki Takei
We compared the sample volume of endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNAB) specimens obtained by 22-gauge (22G) and 25-gauge (25G) needles, and the accuracy rate.This was a retrospective study in a single tertiary referral center. We investigated 153 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent diagnostic EUS-FNAB before neoadjuvant gemcitabine-based chemoradiotherapy between October 2006 and November 2015. We performed immunohistochemical (IHC) analysis of human equilibrative nucleoside transporter 1 using the remnant cell blocks following pathological PDAC diagnosis...
June 2018: Medicine (Baltimore)
Casey Hanson, Junmei Cairns, Liewei Wang, Saurabh Sinha
Recent studies have analyzed large scale data sets of gene expression to identify genes associated with inter-individual variation in phenotypes ranging from cancer sub-types to drug sensitivity, promising new avenues of research in personalized medicine. However, gene expression data alone is limited in its ability to reveal cis-regulatory mechanisms underlying phenotypic differences. In this study, we develop a new probabilistic model, called pGENMi, that integrates multi-omic data to investigate the transcriptional regulatory mechanisms underlying inter-individual variation of a specific phenotype - that of cell line response to cytotoxic treatment...
June 13, 2018: Genome Research
Laura Senier, Catherine Tan, Leandra Smollin, Rachael Lee
PURPOSE: State health agencies (SHAs) have developed public health genomics (PHG) programs that play an instrumental role in advancing precision public health, but there is limited research on their approaches. This study examines how PHG programs attempt to mitigate or forestall health disparities and inequities in the utilization of genomic medicine. METHODS: We compared PHG programs in three states: Connecticut, Michigan, and Utah. We analyzed 85 in-depth interviews with SHA internal and external collaborators and program documents...
June 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Chigusa Morizane, Makoto Ueno, Masafumi Ikeda, Takuji Okusaka, Hiroshi Ishii, Junji Furuse
Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gall bladder, ampullary carcinoma and intrahepatic cholangiocarcinoma are often identified at an advanced stage and have poor prognoses. Although effective chemotherapy regimens are needed, their development remains unsatisfactory. From the results of a phase III clinical trial (ABC-02 trial), gemcitabine plus cisplatin is the standard first-line chemotherapeutic regimen for advanced biliary tract cancer. A phase III trial of gemcitabine plus cisplatin vs...
June 11, 2018: Japanese Journal of Clinical Oncology
Ruzanna Mnatsakanyan, Gerta Shema, Mark Basik, Gerald Batist, Christoph H Borchers, Albert Sickmann, René P Zahedi
Numerous diseases are caused by changes in post-translational modifications (PTMs). Therefore, the number of clinical proteomics studies that include the analysis of PTMs is increasing. Combining complementary information - e.g., changes in protein abundance, PTM levels, with the genome and transcriptome (proteogenomics) - holds great promise for discovering important drivers and markers of disease, as variations in copy number, expression levels, or mutations without spatial/functional/isoform information is often insufficient or even misleading...
June 12, 2018: Expert Review of Proteomics
Dharmesh Gopalakrishnan, Vadim S Koshkin, Moshe C Ornstein, Athanasios Papatsoris, Petros Grivas
Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor. Since the peak incidence of bladder cancer is in the eighth decade of life and beyond, medical comorbidities may often limit the use of chemotherapy. Immune checkpoint inhibitors with their favorable toxicity profiles and notable antitumor activity have ushered in a new era in the treatment of advanced urothelial cancer (UC) with five agents targeting the PD-1/PD-L1 pathway being recently approved by the US Food and Drug administration...
2018: Therapeutics and Clinical Risk Management
Yoosup Chang, Hyejin Park, Hyun-Jin Yang, Seungju Lee, Kwee-Yum Lee, Tae Soon Kim, Jongsun Jung, Jae-Min Shin
In the era of precision medicine, cancer therapy can be tailored to an individual patient based on the genomic profile of a tumour. Despite the ever-increasing abundance of cancer genomic data, linking mutation profiles to drug efficacy remains a challenge. Herein, we report Cancer Drug Response profile scan (CDRscan) a novel deep learning model that predicts anticancer drug responsiveness based on a large-scale drug screening assay data encompassing genomic profiles of 787 human cancer cell lines and structural profiles of 244 drugs...
June 11, 2018: Scientific Reports
G Milano, F Innocenti, B Lacarelle, J Ciccolini
There is a rising evidence that the proverbial statement "No pain, No gain" first coined at the light of pioneering clinical experiences with canonical chemotherapy still holds true in the era of modern treatments of cancer. This close relationship between the occurrence of specific drug-related toxicity and treatment outcome has been confirmed since then with a large variety of treatments, ranging from cytotoxics, hormonotherapy, targeted therapy and much interestingly even with the latest immune checkpoint inhibitors...
July 2018: Critical Reviews in Oncology/hematology
Eoghan Malone, Lillian L Siu
Standard treatment in head and neck squamous cell carcinoma (HNSCC) is limited currently with decisions being made primarily based on tumor location, histology, and stage. The role of the human papillomavirus in risk stratification is actively under clinical trial evaluations. The molecular complexity and intratumoral heterogeneity of the disease are not actively integrated into management decisions of HNSCC, despite a growing body of knowledge in these areas. The advent of the genomic era has delivered vast amounts of information regarding different cancer subtypes and is providing new therapeutic targets, which can potentially be elucidated using next-generation sequencing and other modern technologies...
2018: Clinical Medicine Insights. Oncology
Maliheh Moradzadeh, Azar Hosseini, Hasan Rakhshandeh, Azita Aghaei, Hamid Reza Sadeghnia
Objective: Cuscuta campestris or common dodder is a holoparasitic plant that has been valorized for treatment of liver injury and cancer prevention in traditional medicine. Recently, extract of C. campestris had shown moderate antimicrobial properties and cytotoxic effects. In this study, we examined the level of cellular oxidants, cytotoxicity, apoptosis and differentiation induced by hydroalcoholic extract of C. campestris (CCE) (12.5-200 µg/ml), as well as arsenic trioxide (As2 O3 , 50 µM), in human leukemic (HL60 and NB4) and normal polymorph nuclear cells after 72 hr treatment...
May 2018: Avicenna Journal of Phytomedicine
Michael Untch, Rachel Würstlein, Norbert Marschner, Diana Lüftner, Doris Augustin, Susanne Briest, Johannes Ettl, Renate Haidinger, Lothar Müller, Volkmar Müller, Eugen Ruckhäberle, Nadia Harbeck, Christoph Thomssen
The fourth international advanced breast cancer consensus conference (ABC4) on the diagnosis and treatment of advanced breast cancer (ABC) headed by Professor Fatima Cardoso was once again held in Lisbon on November 2 - 4, 2017. To simplify matters, the abbreviation ABC will be used hereinafter in the text. In clinical practice, the abbreviation corresponds to metastatic breast cancer or locally far-advanced disease. This year the focus was on new developments in the treatment of ABC. Topics discussed included the importance of CDK4/6 inhibition in hormone receptor (HR)-positive ABC, the use of dual antibody blockade to treat HER2-positive ABC, PARP inhibition in triple-negative ABC and the potential therapeutic outcomes...
May 2018: Geburtshilfe und Frauenheilkunde
Anna Song, Wankyu Eo, Sehyun Kim, Bumsang Shim, Sookyung Lee
BACKGROUND: Advanced hepatobiliary cancers are highly lethal cancers that require precise prediction in clinical practice. Serum ferritin level increases in malignancy and high serum ferritin level is associated with poor survival in various cancers. This study aimed to identify whether serum ferritin could independently predict the overall survival (OS) of patients with advanced hepatobiliary cancers. METHODS: The retrospective cohort study was performed by reviewing medical records of patients with advanced hepatobiliary cancers from June 2006 to September 2016...
June 7, 2018: BMC Complementary and Alternative Medicine
E Dahl
BACKGROUND: Over the last 15 years, an estimated 3000 large centralized biobanks have been established worldwide, making important contributions to the further development of precision medicine. In many cases, these biobanks are affiliated with pathological institutes or work closely with them. OBJECTIVE: In which translational research projects, and during which phases in the development of new drugs are human bioprobes being used and can their use be easily traced in the literature? METHODS: PubMed, Internet research, and information from the German Biobank Alliance and the European initiative BBMRI-ERIC...
June 6, 2018: Der Pathologe
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