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Precision Medicine In Cancer

Wei Zhan, Celeste A Shelton, Phil J Greer, Randall E Brand, David C Whitcomb
Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate the oncogenic process. We systematically reviewed, annotated, and classified previously reported pancreatic cancer-associated germline variants in established risk genes. Variants were scored using multiple criteria and binned by evidence for pathogenicity, then annotated with published functional studies and associated biological systems/pathways...
September 2018: Pancreas
E F Gaffney, P H Riegman, W E Grizzle, P H Watson
The decision to use 10% neutral buffered formalin fixed, paraffin embedded (FFPE) archival pathology material may be dictated by the cancer research question or analytical technique, or may be governed by national ethical, legal and social implications (ELSI), biobank, and sample availability and access policy. Biobanked samples of common tumors are likely to be available, but not all samples will be annotated with treatment and outcomes data and this may limit their application. Tumors that are rare or very small exist mostly in FFPE pathology archives...
August 16, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
Yifei Dai, Liang Sun, Weijie Qiang
Currently, cancer has become one of the major refractory diseases threatening human health. Complementary and alternative medicine (CAM) has gradually become an alternative choice for patients, which can be attributed to the high cost of leading cancer treatments (including surgery, radiotherapy, and chemotherapy) and the severe related adverse effects. As a critical component of CAM, traditional Chinese medicine (TCM) has increasing application in preventing and treating cancer over the past few decades. Huanglian Jiedu Decoction (HJD), a classical Chinese compound formula, has been recognized to exert a beneficial effect on cancer treatment, with few adverse effects reported...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Imke H Bartelink, Ella F Jones, Sheerin K Shahidi-Latham, Evelyn Lee Pei Rong, Yanan Zheng, Paolo Vicini, Laura van 't Veer, Denise Wolf, Andrei Iagaru, Deanna L Kroetz, Brendan Prideaux, Cornelius Cilliers, Greg Thurber, Zena Wimana, Geraldine Gebhart
Precision medicine aims to use patient genomic, epigenomic, specific drug dose and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State-of-the-art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement and expression of pharmacological activity. Using In silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome...
August 14, 2018: Clinical Pharmacology and Therapeutics
Hang Wang, Jianing Xi, Minghui Wang, Ao Li
An effective way to facilitate the development of modern oncology precision medicine is the systematical analysis of the known drug sensitivities that have emerged in recent years. Meanwhile, the screening of drug response in cancer cell lines provides an estimable genomic and pharmacological data towards high accuracy prediction. Existing works primarily utilize genomic or functional genomic features to classify or regress the drug response. Here in this work, by the migration and extension of the conventional merchandise recommendation methods, we introduce an innovation model on accurate drug sensitivity prediction by using dual-layer strengthened collaborative topic regression (DS-CTR), which incorporates not only the graphic model to jointly learn drugs and cell lines feature from pharmacogenomics data but also drug and cell line similarity network model to strengthen the correlation of the prediction results...
August 10, 2018: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Stefan Rutkowski, Piergiorgio Modena, Daniel Williamson, Kornelius Kerl, Karsten Nysom, Barry Pizer, Ute Bartels, Stephanie Puget, François Doz, Antony Michalski, Katja von Hoff, Mathilde Chevignard, Shivaram Avula, Matthew J Murray, Stefan Schönberger, Thomas Czech, Antoinette Y N Schouten-van Meeteren, Uwe Kordes, Christof M Kramm, Dannis G van Vuurden, Esther Hulleman, Geert O Janssens, Guirish A Solanki, Marie-Luise C van Veelen, Ulrich Thomale, Martin U Schuhmann, Chris Jones, Felice Giangaspero, Dominique Figarella-Branger, Torsten Pietsch, Steve C Clifford, Stefan M Pfister, Stefaan W Van Gool
Paediatric CNS tumours are the most common cause of childhood cancer-related morbidity and mortality, and improvements in their diagnosis and treatment are needed. New genetic and epigenetic information about paediatric CNS tumours is transforming the field dramatically. For most paediatric CNS tumour entities, subgroups with distinct biological characteristics have been identified, and these characteristics are increasingly used to facilitate accurate diagnoses and therapeutic recommendations. Future treatments will be further tailored to specific molecular subtypes of disease, specific tumour predisposition syndromes, and other biological criteria...
August 2018: Lancet Oncology
Jean-Louis Pujol, Benoît Roch, Camille N Pujol, Catherine Goze
Small cell lung cancer accounts for 14% of all lung cancers. It remains a major challenge for oncology as the progresses made in the past three decades are modest. After a rapid overview of current knowledge regarding somatic genomic alterations, this state-of-art addresses pathways to improve small-cell lung cancer outcome such as the targeting of DNA damage repair mechanisms firstly anti-PARPs, inhibitory molecules of EZH2, derepression of the NOTCH pathway, rovalbituzumab-tesirine, inhibition of serine/threonine Aurora A kinase, temozolomide and its dependence on methylation of the MGMT promoter...
August 9, 2018: Bulletin du Cancer
Altaf Mohammed, Nagendra Sastry Yarla, Venkateshwar Madka, Chinthalapally V Rao
Substantial efforts are underway for prevention of early stages or recurrence of colorectal cancers (CRC) or new polyp formation by chemoprevention strategies. Several epidemiological, clinical and preclinical studies to date have supported the chemopreventive potentials of several targeted drug classes including non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, naproxen, sulindac, celecoxib, and licofelone), statins and other natural agents-both individually, and in combinations. Most preclinical trials although were efficacious, only few agents entered clinical trials and have been proven to be potential chemopreventive agents for colon cancer...
August 8, 2018: International Journal of Molecular Sciences
Gilbert Bigras, Simon Mairs, Paul E Swanson, Didier Morel, Raymond Lai, Iyare Izevbaye
Pembrolizumab is an FDA-approved immune-checkpoint (IC) inhibitor that targets programmed cell death protein PD-1, and recent phase III trials have demonstrated its superiority over chemotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Eligibility for treatment with Pembrolizumab is based on demonstration of PD-L1 expression on tumoral cells using the approved companion test 22C3 PharmDx (Dako). Access to the drug depends on a tumor proportion score (TPS) expressing the PD-L1 protein above predetermined cutoffs...
August 8, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Nooshin Hashemi-Sadraei, Gaëlle M Müller-Greven, Fadi W Abdul-Karim, Ilya Ulasov, Erinn Downs-Kelly, Monica E Burgett, Adam Lauko, Maha A Qadan, Robert J Weil, Manmeet S Ahluwalia, Lingling Du, Richard A Prayson, Samuel T Chao, Thomas G Budd, Jill Barnholtz-Sloan, Amy S Nowacki, Ruth A Keri, Candece L Gladson
BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer...
August 9, 2018: Journal of Neuro-oncology
Juan Jovel, Zhen Lin, Sandra O'keefe, Steven Willows, Weiwei Wang, Guangzhi Zhang, Jordan Patterson, Carlos Moctezuma-Velázquez, David J Kelvin, Gane Ka-Shu Wong, Andrew L Mason
Understanding the heterogeneity of dysregulated pathways associated with the development of hepatocellular carcinoma (HCC) may provide prognostic and therapeutic avenues for disease management. As HCC involves a complex process of genetic and epigenetic modifications, we evaluated expression of both polyadenylated transcripts and microRNAs from HCC and liver samples derived from two cohorts of patients undergoing either partial hepatic resection or liver transplantation. Copy number variants were inferred from whole genome low-pass sequencing data, and a set of 56 cancer-related genes were screened using an oncology panel assay...
August 2018: Hepatology Communications
Han Zhang, Litao Sun
The human microbiota interacts with the host immune system in multiple ways to influence the development of diseases, including cancers; however, a detailed understanding of their relationship is unavailable. Accumulating evidence has only revealed an association rather than a causal link between microbial alterations and carcinogenesis. The regulatory loops among the microbiome, human cells and the immune system are far more complicated and require further studies to be revealed. In this review, we discuss the impact of the microbiota on cancer initiation, development and progression in different types of human cells, mainly focusing on the clinical translation from microbiome research to an accurate diagnosis, subtype classification and precision medicine...
2018: American Journal of Cancer Research
Christian Rolfo, Paolo Manca, Roberto Salgado, Peter Van Dam, Amelie Dendooven, Andreia Machado Coelho, Jose Ferri Gandia, Annemie Rutten, Willem Lybaert, Joanna Vermeij, Thomas Gevaert, Christine Weyn, Anneke Lefebure, Sofie Metsu, Steven Van Laere, Marc Peeters, Patrick Pauwels
Background: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network. Materials and methods: Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit...
2018: ESMO Open
Marc van der Schee, Hazel Pinheiro, Edoardo Gaude
Breath biopsy enables the non-invasive collection and analysis of volatile organic compounds (VOCs) in exhaled breath, providing valuable information about disease processes occurring in the body. Metabolic changes occur in cancer cells at the earliest stages of disease. We discuss progress in the use of breath biopsy for discovery of breath-based biomarkers for early detection of cancer, and potential applications for breath biopsy in enabling precision medicine in cancer.
2018: Ecancermedicalscience
Neda Stjepanovic, Tracy L Stockley, Philippe L Bedard, Jeanna M McCuaig, Melyssa Aronson, Spring Holter, Kara Semotiuk, Natasha B Leighl, Raymond Jang, Monika K Krzyzanowska, Amit M Oza, Abha Gupta, Christine Elser, Lailah Ahmed, Lisa Wang, Suzanne Kamel-Reid, Lillian L Siu, Raymond H Kim
BACKGROUND: Matched tumor-normal sequencing, applied in precision cancer medicine, can identify unidentified germline Medically Actionable Variants (gMAVS) in cancer predisposition genes. We report patient preferences for the return of additional germline results, and describe various gMAV scenarios delivered through a clinical genetics service. METHODS: Tumor profiling was offered to 1960 advanced cancer patients, of which 1556 underwent tumor-normal sequencing with multigene hotspot panels containing 20 cancer predisposition genes...
August 9, 2018: BMC Medical Genomics
Ageliki Laina, Aikaterini Gatsiou, Georgios Georgiopoulos, Kimon Stamatelopoulos, Konstantinos Stellos
Since our knowledge on structure and function of messenger RNA (mRNA) has expanded from merely being an intermediate molecule between DNA and proteins to the notion that RNA is a dynamic gene regulator that can be modified and edited, RNA has become a focus of interest into developing novel therapeutic schemes. Therapeutic modulation of RNA molecules by DNA- and RNA-based therapies has broadened the scope of therapeutic targets in infectious diseases, cancer, neurodegenerative diseases and most recently in cardiovascular diseases as well...
2018: Frontiers in Physiology
Sung Noh Hong
Colorectal cancer (CRC) arise from multi-step carcinogenesis due to genetic mutations and epigenetic modifications of human genome. Genetic mutations and epigenetic modifications were originally established as 2 independent mechanisms contributing to colorectal carcinogenesis. However, recent evidences demonstrate that there are interactions between these 2 mechanisms. Genetic mutations enable disruption of epigenetic controls while epigenetic modifications can initiate genomic instability and carcinogenesis...
July 2018: Intestinal Research
Oz Mordechai, Myriam Weyl-Ben-Arush
OBJECTIVE: To date, the understanding of pediatric tumor genomics and how these genetic aberrations correlate with clinical outcome is lacking. Here, we report our experience with the next-generation sequencing (NGS) test program and discuss implications for the inclusion of molecular profiling into clinical pediatric oncology trials. We also aimed to explore studies on NGS in pediatric cancers and to quantify the variability of finding actionable mutations and the clinical implications...
July 30, 2018: Rambam Maimonides Medical Journal
Diego Cortinovis, Stefania Canova, Maria I Abbate, Francesca Colonese, Viola Cogliati, Paolo Bidoli
ALK positivity, despite representing only in a small proportion of patients with non-small-cell lung cancer, is worth researching at diagnosis given the possibility to treat these patients with some targeted ALK inhibitors, which are more potent than chemotherapy. Thanks to understanding the resistance mechanisms, newer and more selective inhibitors are now available in clinical practice. Hence, this disease represents, after EGFR inhibition, a largely effective precision medicine approach. However, there are still some clinical situations in which the targeted drug seems to be ineffective...
August 8, 2018: Future Oncology
Laura Muinelo-Romay, Carlos Casas-Arozamena, Miguel Abal
The identification of new molecular targets and biomarkers associated with high risk of recurrence and response to therapy represents one of the main clinical challenges in the management of advanced disease in endometrial cancer. In this sense, the field of liquid biopsy has emerged as a great revolution in oncology and is considered "the way" to reach personalised medicine. In this review, we discuss the promising but already relatively limited advances of liquid biopsy in endometrial cancer compared to other types of tumours like breast, colorectal or prostate cancer...
August 7, 2018: International Journal of Molecular Sciences
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