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Trends in Cancer

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https://www.readbyqxmd.com/read/30292353/emerging-contributions-of-cancer-testis-antigens-to-neoplastic-behaviors
#1
REVIEW
Zane A Gibbs, Angelique W Whitehurst
Tumors of nearly every origin activate the expression of genes normally restricted to gametogenic cells. These genes encode proteins termed cancer/testis (CT) antigens, since expression outside of their naturally immune-privileged site can evoke an immune response. Despite extensive efforts to exploit CT antigens as immunotherapeutic targets, investigation of whether these proteins participate in tumorigenic processes has lagged. Here, we discuss emerging evidence that demonstrates that CT antigens can confer a selective advantage to tumor cells by promoting oncogenic processes or permitting evasion of tumor-suppressive mechanisms...
October 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30292352/trinucleotide-repeat-expansion-diseases-rnai-and-cancer
#2
REVIEW
Andrea E Murmann, Jindan Yu, Puneet Opal, Marcus E Peter
Many neurodegenerative diseases are caused by unstable trinucleotide repeat (TNR) expansions located in disease-associated genes. siRNAs based on CAG repeat expansions effectively kill cancer cell lines in vitro through RNAi. They also cause significant reduction in tumor growth in a human ovarian cancer mouse model with no toxicity to the treated mice. This suggests that cancer cells are particularly sensitive to CAG TNR-derived siRNAs, and explains a reported inverse correlation between the length of CAG TNRs and reduced global cancer incidences in some CAG TNR diseases...
October 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30292351/synthetic-lethality-and-cancer-penetrance-as-the-major-barrier
#3
REVIEW
Colm J Ryan, Ilirjana Bajrami, Christopher J Lord
Synthetic lethality has long been proposed as an approach for targeting genetic defects in tumours. Despite a decade of screening efforts, relatively few robust synthetic lethal targets have been identified. Improved genetic perturbation techniques, including CRISPR/Cas9 gene editing, have resulted in renewed enthusiasm for searching for synthetic lethal effects in cancer. An implicit assumption behind this enthusiasm is that the lack of reproducibly identified targets can be attributed to limitations of RNAi technologies...
October 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30292350/are-microbial-endophytes-the-actual-producers-of-bioactive-antitumor-agents
#4
REVIEW
David J Newman
For millenia, plants have been a major source of medications against human and animal diseases. In the case of anticancer agents, a significant number of current agents can trace their source back to nominally plant secondary metabolites, with examples being taxol, vinca alkaloids, camptothecin (CPT), and their modified derivatives. However, it is now becoming apparent that these and other plant-derived materials, plus similar agents from marine sources may well have a microbe in their background. In this short Opinion, evidence for such claims are presented for some of the agents currently in use or in preclinical and clinical trials against cancer...
October 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30292349/mutation-signatures-depend-on-epigenomic-contexts
#5
Neil Coleman, Subhajyoti De
Mutation signatures - the patterns of acquired genetic changes in somatic genomes - provide critical insights into DNA repair defects and exposure to mutagenic processes during development, aging, and cancer progression. Efforts to decipher the etiology of the emerging computationally predicted mutation signatures in cancer genomes are currently underway. Since chromatin and epigenomic contexts influence DNA damage and repair pathway choices, taking both epigenomic and sequence contexts of the mutations into consideration is likely to benefit interpretation of mutation signatures...
October 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30292348/lighting-up-cancer-dynamics
#6
Pavithran T Ravindran, Maxwell Z Wilson
Live-cell microscopy has revealed that signaling pathways carry elaborate time-varying activities. Yet, the connection between these dynamics and cellular disease has remained elusive. Recent work leverages cellular optogenetics to analyze the Ras-to-Erk transfer function in cancer cells. These analyses reveal how changes to the filtering properties of a pathway lead to the misperception of extracellular events. Overall, these studies suggest that mutations do not simply hyperactivate pathways but rather can also change their transmission properties in more subtle ways...
October 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30292347/we-are-all-connected-modeling-the-tumor-immune-ecosystem
#7
Jonathan D Schoenfeld
Circulating tumor-reactive immune cells link tumor responses at anatomically distant locations, yet this interconnectedness is poorly understood on a macro level. Can we use mathematical models to better understand these complex relationships? Recent work provides a framework to evaluate the effects that T cells generated at one site may have on metastases elsewhere in the body and suggests that in the era of immunotherapy the concept of 'local' therapy needs to be refined.
October 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30149882/improving-cancer-detection-and-treatment-with-liquid-biopsies-and-ptdna
#8
REVIEW
Michael D Kessler, Nisha R Pawar, Stuart S Martin, Toni M Antalis, Timothy D O'Connor
Liquid biopsy, or the capacity to noninvasively isolate and analyze plasma tumor DNA (ptDNA) using blood samples, represents an important tool for modern oncology that enables increasingly safe, personalized, and robust cancer diagnosis and treatment. Here, we review advances in the development and implementation of liquid biopsy approaches, and we focus on the capacity of liquid biopsy to noninvasively detect oncological disease and enhance early detection strategies. In addition to noting the distinctions between mutation-targeted and mutation-agnostic approaches, we discuss the potential for genomic analysis and longitudinal testing to identify somatic lesions early and to guide intervention at more manageable disease stages...
September 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30149881/personalized-cancer-models-for-target-discovery-and-precision-medicine
#9
REVIEW
Carla Grandori, Christopher J Kemp
Although cancer research is progressing at an exponential rate, translating this knowledge to develop better cancer drugs and more effectively match drugs to patients is lagging. Genome profiling of tumors provides a snapshot of the genetic complexity of individual tumors, yet this knowledge is insufficient to guide therapy for most patients. Model systems, usually cancer cell lines or mice, have been instrumental in cancer research and drug development, but translation of results to the clinic is inefficient, in part, because these models do not sufficiently reflect the complexity and heterogeneity of human cancer...
September 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30149880/protein-protein-interactions-emerging-oncotargets-in-the-ras-erk-pathway
#10
REVIEW
Rocío García-Gómez, Xosé R Bustelo, Piero Crespo
Given the implication of aberrant RAS-extracellular signal-regulated kinase (ERK) signaling in the development of a large number of tumor types, this route is under intense scrutiny to identify new anticancer drugs. Most avenues in that direction have been primarily focused on the inhibition of the catalytic activity of the kinases that participate in this pathway. Although promising, the efficacy of these therapies is short lived due to undesired toxicity and/or drug resistance problems. As an alternative path, new efforts are now being devoted to the targeting of protein-protein interactions (PPIs) involved in the flow of RAS-ERK signals...
September 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30149879/balancing-the-economics-and-ethics-of-personalised-oncology
#11
REVIEW
Nicola Flaum, Peter Hall, Christopher McCabe
The cost of personalised medicine in oncology is increasing. The varied and contrasting priorities of the pharmaceutical industry, local and national governments, international medical community, and patients need to be reviewed and balanced. In addition to the economic and political standpoints on this issue, the ethical considerations from physicians' viewpoints need to be considered to optimise cancer patients' care. In this paper we discuss the way research and development (R&D) of these drugs is carried out and reimbursed, and how this needs to change...
September 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30149878/perspectives-on-idh-mutation-in-diffuse-gliomas
#12
Yu-Ting Su, Funita P Phan, Jing Wu
Isocitrate dehydrogenase (IDH) mutations are biomarkers to classify diffuse gliomas into biologically similar subgroups. Tremendous efforts have been made to understand the biology of IDH-mutant gliomas at the genetic, epigenetic, transcriptional, and protein levels. Preclinical models that recapitulate human tumor biology are crucial not only to our understanding of IDH mutations in gliomagenesis, but also in testing of novel therapeutic agents that may lead to more effective therapies for IDH-mutant glioma patients...
September 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30149877/mdm2-tp53-crossregulation-an-underestimated-target-to-promote-loss-of-tp53-function-and-cell-survival
#13
T Soussi, G Kroemer
Half of human cancers bear inactivating mutations of the tumor suppressor gene TP53, but the other half do not. In a recent issue of Cancer Cell, Dhar et al. and Zhu et al. reported that, in liver cancer and medulloblastoma, MDM2 is constitutively activated, causing a loss of TP53 function that does not require TP53 mutation. On theoretical grounds, such cancer would be amenable to treatment with MDM2 inhibitors.
September 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30149876/modeling-tumor-immunology-and-immunotherapy-in-mice
#14
Aitziber Buqué, Lorenzo Galluzzi
Figure 1. Main Applications of Mouse Models for Tumor Immunology and Immunotherapy. Immunodeficient mice xenografted with human cancer cell lines have been at the foundation of in vivo cancer research for several decades, providing ground for the regulatory approval of multiple chemotherapeutics and targeted anticancer agents, but are intrinsically unsuitable for studying tumor immunology and immunotherapy. Similarly, patient-derived xenografts (PDXs) established in immunodeficient mice are not subjected to immunosurveillance by the host, although (depending on the protocol employed for PDX generation) some components of the patient's immune system may also be transferred to the mouse and be active, at least for some time...
September 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30064665/deregulation-of-retroelements-as-an-emerging-therapeutic-opportunity-in-cancer
#15
REVIEW
Charles A Ishak, Marie Classon, Daniel D De Carvalho
Nearly half of the human genome is comprised of repetitive elements that are tightly regulated to protect the host genome from deleterious consequences associated with their inappropriate activation. Cancer cells often misexpress these elements, in part, due to decreases in DNA methylation. Recent discoveries suggest that tumor suppressor proteins contribute to repression of repetitive elements, and their functional inactivation promotes repeat element misexpression during carcinogenesis. Recent findings also suggest that increased expression of repetitive elements beyond a threshold of tolerance can augment cancer therapy responses...
August 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30064664/seeking-convergence-and-cure-with-new-myeloma-therapies
#16
REVIEW
Priya Choudhry, Derek Galligan, Arun P Wiita
For over a decade, the mainstay of multiple myeloma therapy has been small molecules that directly attack malignant plasma cell biology. However, potent immunotherapies have recently emerged, transforming the myeloma therapeutic landscape. Here we first review new promising strategies to target plasma cells through protein homeostasis and epigenetic modulators. We then discuss emerging immunotherapy strategies that are leading to dramatic results in patients. Finally, we focus on recent preclinical data suggesting that enforcing cell-surface antigen expression through small molecules may enhance immunotherapy efficacy and avoid resistance...
August 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30064663/epigenetic-mechanisms-dictating-eradication-of-cancer-by-natural-killer-cells
#17
REVIEW
Suresh Bugide, Radoslav Janostiak, Narendra Wajapeyee
Natural killer (NK) cells of the innate immune system are the first line of defense against infectious agents and cancer cells. However, only a few mechanisms that regulate eradication of tumors by NK cells have been identified. In this review, we present an account of epigenetic mechanisms that modulate the ability of NK cells to eradicate cancer cells. To date, several drugs that target epigenetic modifiers have shown clinical efficacy in cancer. Therefore, once a given epigenetic modifier is validated as a regulator of NK cell function, it can be targeted for NK cell-based cancer immunotherapies...
August 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30064662/glycosylation-and-integrin-regulation-in-cancer
#18
REVIEW
Grazia Marsico, Laura Russo, Fabio Quondamatteo, Abhay Pandit
Integrins are transmembrane receptors that coordinate extracellular matrix (ECM)-cell and cell-cell interactions, signal transmission, gene expression, and cell function. The aberration of integrin function is one of the well-recognized mechanisms of cancer. The activity of integrins is strongly influenced by glycans through glycosylation events and the establishment of glycan-mediated interactions. Glycans represent a class of ubiquitous biomolecules that display an extraordinary complexity and diversity in both structure and function...
August 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30064661/the-making-of-a-precancer-atlas-promises-challenges-and-opportunities
#19
REVIEW
Sudhir Srivastava, Sharmistha Ghosh, Jacob Kagan, Richard Mazurchuk
Many cancers evolve from benign precancerous lesions and have a natural history of progression that provides a window of opportunity for intervention. The biological mechanisms underlying this evolutionary trajectory can only be truly understood through an extensive characterization of the molecular, cellular, and non-cellular properties of premalignant and malignant tumors, and must also recognize how the microenvironment (stromal cells, immune cells, and other types of cells) contributes to this evolution...
August 2018: Trends in Cancer
https://www.readbyqxmd.com/read/30064660/exit-stage-left-a-tumor-cell-s-journey-from-lymph-node-to-beyond
#20
Marc G Achen, Steven A Stacker
Even though we have known for over 250 years that cancers spread to regional lymph nodes (LNs) and distant organs, the fundamental question of which anatomical routes are taken by tumor cells has remained a mystery. Two recently published papers in Science, by Pereira et al. and Brown et al., directly address this important issue in tumor biology by assessing the capacity of tumor cells in LNs to spread to distant sites.
August 2018: Trends in Cancer
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