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Trends in Cancer

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https://www.readbyqxmd.com/read/29458967/improving-cancer-immunotherapies-through-empirical-neoantigen-selection
#1
Catarina Nogueira, Johanna K Kaufmann, Hubert Lam, Jessica B Flechtner
Targeting neoantigens has become an attractive strategy for cancer immunotherapy. Epitope prediction algorithms facilitate rapid selection of potential neoantigens, but are plagued with high false-positive and false-negative rates. Here we review ex vivo technologies for biological identification of neoantigens to improve empirical prioritization for immunotherapy.
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29458966/have-clinical-trials-properly-assessed-c-met-inhibitors
#2
Veronica S Hughes, Dietmar W Siemann
The c-Met/HGF pathway is implicated in cancer progression and dissemination. Many inhibitors have been developed to target this pathway. Unfortunately, most trials have failed to demonstrate efficacy. However, clinical trials have not adequately tested the concept of c-Met pathway inhibition due to the lack of appropriate patient selection criteria.
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29458965/the-sympathetic-nervous-system-drives-tumor-angiogenesis
#3
Hubert Hondermarck, Phillip Jobling
Neurobiology is increasingly contributing to cancer research. Recent work indicates that noradrenaline released by sympathetic adrenergic nerves in prostate cancer can stimulate β-adrenoceptors in endothelial cells. This leads to the alteration of endothelial cell metabolism toward the inhibition of oxidative phosphorylation and the induction of an angiogenic switch that fuels cancer progression. These findings suggest that the sympathetic nervous system is a higher-level control of tumor angiogenesis that could be targeted in clinical oncology...
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29458964/metabolism-activity-and-targeting-of-d-and-l-2-hydroxyglutarates
#4
REVIEW
Dan Ye, Kun-Liang Guan, Yue Xiong
Isocitrate dehydrogenases (IDH1/2) are frequently mutated in multiple types of human cancer, resulting in neomorphic enzymes that convert α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG). The current view on the mechanism of IDH mutation holds that 2-HG acts as an antagonist of α-KG to competitively inhibit the activity of α-KG-dependent dioxygenases, including those involved in histone and DNA demethylation. Recent studies have implicated 2-HG in activities beyond epigenetic modification. Multiple enzymes have been discovered that lack mutations but that can nevertheless produce 2-HG promiscuously under hypoxic or acidic conditions...
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29458963/b-cell-metabolic-remodeling-and-cancer
#5
REVIEW
Davide G Franchina, Melanie Grusdat, Dirk Brenner
Cells of the immune system display varying metabolic profiles to fulfill their functions. B lymphocytes overcome fluctuating energy challenges as they transition from the resting state and recirculation to activation, rapid proliferation, and massive antibody production. Only through a controlled interplay between metabolism, extracellular stimuli, and intracellular signaling can successful humoral responses be mounted. Alterations to this balance can promote malignant transformation of B cells. The metabolic control of B-cell fate is only partially understood...
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29458962/re-emergence-of-dendritic-cell-vaccines-for-cancer-treatment
#6
REVIEW
Mansi Saxena, Nina Bhardwaj
Dendritic cells (DCs) are essential in immunity owing to their role in activating T cells, thereby promoting antitumor responses. Tumor cells, however, hijack the immune system, causing T cell exhaustion and DC dysfunction. Tumor-induced T cell exhaustion may be reversed through immune checkpoint blockade (ICB); however, this treatment fails to show clinical benefit in many patients. While ICB serves to reverse T cell exhaustion, DCs are still necessary to prime, activate, and direct the T cells to target tumor cells...
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29458961/the-genetic-non-genetic-duality-of-drug-resistance-in-cancer
#7
REVIEW
Ravi Salgia, Prakash Kulkarni
Drug resistance is a serious impediment to the treatment of cancer. However, the mechanisms involved remain poorly understood. While it is widely held that the phenomenon is genetic in nature, emerging evidence suggests that non-genetic mechanisms may also be important. Furthermore, at least in some cases, refractoriness to treatment can be reversed by epigenetic reprogramming, and combination and intermittent therapies, as opposed to sustained monotherapy, appear more effective in attenuating it. Here we iterate the confusion in understanding the phenomenon by which cancer cells evade drug response and underscore the need to recognize the genetic/non-genetic duality of drug resistance in cancer...
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29458960/challenging-standard-of-care-paradigms-in-the-precision-oncology-era
#8
REVIEW
Vivek Subbiah, Razelle Kurzrock
The pace of genomic and immunological breakthroughs in oncology is accelerating, making it likely that large randomized trials will increasingly become outdated before their completion. Traditional clinical research/practice paradigms must adapt to the reality unveiled by genomics, especially the need for customized drug combinations, rather than one-size-fits-all monotherapy. The raison-d'être of precision oncology is to offer 'the right drug for the right patient at the right time', a process enabled by transformative tissue and blood-based genomic technologies...
February 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413424/gastrointestinal-stromal-tumors-the-gist-of-precision-medicine
#9
REVIEW
Lin Mei, Steven C Smith, Anthony C Faber, Jonathan Trent, Steven R Grossman, Constantine A Stratakis, Sosipatros A Boikos
The discovery of activated KIT mutations in gastrointestinal (GI) stromal tumors (GISTs) in 1998 triggered a sea change in our understanding of these tumors and has ushered in a new paradigm for the use of molecular genetic diagnostics to guide targeted therapies. KIT and PDGFRA mutations account for 85-90% of GISTs; subsequent genetic studies have led to the identification of mutation/epimutation of additional genes, including the succinate dehydrogenase (SDH) subunit A, B, C, and D genes. This review focuses on integrating findings from clinicopathologic, genetic, and epigenetic studies, which classify GISTs into two distinct clusters: an SDH-competent group and an SDH-deficient group...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413423/genomic-landscape-of-pheochromocytoma-and-paraganglioma
#10
Ivana Jochmanova, Karel Pacak
Recent comprehensive molecular analysis allowed the identification of unique molecular signatures in pheochromocytomas (PHEOs) and paragangliomas (PGLs). Here we summarize the main pathway clusters activated by PHEO- and PGL-susceptibility genes: pseudohypoxic, kinase, and Wnt signaling. Molecular characterization and clustering of PHEOs and PGLs may help in the application of principles of personalized medicine and in decision making for targeted therapy of these tumors.
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413422/prc1-linking-cytokinesis-chromosomal-instability-and-cancer-evolution
#11
REVIEW
Jing Li, Marlene Dallmayer, Thomas Kirchner, Julian Musa, Thomas G P Grünewald
Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413421/inflammatory-reprogramming-with-ido1-inhibitors-turning-immunologically-unresponsive-cold-tumors-hot
#12
REVIEW
George C Prendergast, Arpita Mondal, Souvik Dey, Lisa D Laury-Kleintop, Alexander J Muller
We discuss how small-molecule inhibitors of the tryptophan (Trp) catabolic enzyme indoleamine 2,3-dioxygenase (IDO) represent a vanguard of new immunometabolic adjuvants to safely enhance the efficacy of cancer immunotherapy, radiotherapy, or 'immunogenic' chemotherapy by leveraging responses to tumor neoantigens. IDO inhibitors re-program inflammatory processes to help clear tumors by blunting tumor neovascularization and restoring immunosurveillance. Studies of regulatory and effector pathways illuminate IDO as an inflammatory modifier...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413420/transforming-biomarker-development-with-exceptional-responders
#13
Philip Jonsson, Barry S Taylor
Curative therapy for cancer patients with advanced-stage disease remains elusive. While rare outlier responses to anticancer therapies exist, barriers limit our understanding of the molecular and genetic basis of such profound, life-altering responses. Here, we describe how phenotype-to-genotype studies are elucidating the molecular underpinnings of outlier responses and informing strategies to extend such unprecedented sensitivity to broader molecularly defined patient populations.
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413419/dissemination-from-a-solid-tumor-examining-the-multiple-parallel-pathways
#14
REVIEW
Moriah E Katt, Andrew D Wong, Peter C Searson
Metastasis can be generalized as a linear sequence of events whereby halting one or more steps in the cascade may reduce tumor cell dissemination and ultimately improve patient outcomes. However, metastasis is a complex process with multiple parallel mechanisms of dissemination. Clinical strategies focus on removing the primary tumor and/or treating distant metastases through chemo- or immunotherapies. Successful strategies for blocking metastasis will need to address the parallel mechanisms of dissemination and identify common bottlenecks...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413418/dise-a-seed-dependent-rnai-off-target-effect-that-kills-cancer-cells
#15
REVIEW
William Putzbach, Quan Q Gao, Monal Patel, Ashley Haluck-Kangas, Andrea E Murmann, Marcus E Peter
Off-target effects (OTEs) represent a significant caveat for RNAi caused by substantial complementarity between siRNAs and unintended mRNAs. We now discuss the existence of three types of seed-dependent OTEs (sOTEs). Type I involves unintended targeting through the guide strand seed of an siRNA. Type II is caused by the activity of the seed on the designated siRNA passenger strand when loaded into the RNA-induced silencing complex (RISC). Both type I and II sOTEs will elicit unpredictable cellular responses...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29413417/clinical-trials-transparency-where-are-we-today
#16
Rafael Dal-Ré
To prevent reporting bias, policies and regulations mandating trial prospective registration and disclosure of results have been implemented since 2005. To achieve full trial transparency, open access to participants' deidentified data policies have been issued. Funders and journals have made critical decisions on these requirements in 2017 that will impact the current scenario.
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29198442/biology-informs-treatment-choices-in-diffuse-large-b-cell-lymphoma
#17
REVIEW
Matthew J Butler, Ricardo C T Aguiar
The effective deployment of rationally developed therapies for diffuse large B cell lymphoma (DLBCL) requires rapid assimilation of new biological data. Within this framework, here we address topical issues at the intersection of DLBCL biology and the clinic. We discuss targeting of B cell receptor (BCR) signaling, with emphasis on identifying patients who may benefit from this maneuver and how to best achieve it. We address strategies to modulate the DLBCL microenvironment, including the use of immune checkpoint inhibitors in selected DLBCL subsets, and the potential activity of alternative antiangiogenic therapies...
December 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29198441/mitochondria-bioenergetics-and-apoptosis-in-cancer
#18
REVIEW
Peter J Burke
Until recently, the dual roles of mitochondria in ATP production (bioenergetics) and apoptosis (cell life/death decision) were thought to be separate. New evidence points to a more intimate link between these two functions, mediated by the remodeling of the mitochondrial ultrastructure during apoptosis. While most of the key molecular players that regulate this process have been identified (primarily membrane proteins), the exact mechanisms by which they function are not yet understood. Because resistance to apoptosis is a hallmark of cancer, and because ultimately all chemotherapies are believed to result directly or indirectly in induction of apoptosis, a better understanding of the biophysical processes involved may lead to new avenues for therapy...
December 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29198440/fanconi-anemia-signaling-and-cancer
#19
REVIEW
Manoj Nepal, Raymond Che, Jun Zhang, Chi Ma, Peiwen Fei
The extremely high cancer incidence associated with patients suffering from a rare human genetic disease, Fanconi anemia (FA), demonstrates the importance of FA genes. Over the course of human tumor development, FA genes perform critical tumor-suppression roles. In doing so, FA provides researchers with a unique genetic model system to study cancer etiology. Here, we review how aberrant function of the 22 FA genes and their signaling network contributes to malignancy. From this perspective, we will also discuss how the knowledge discovered from FA research serves basic and translational cancer research...
December 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29198439/mitochondrial-transfer-in-the-leukemia-microenvironment
#20
REVIEW
Emmanuel Griessinger, Ruxanda Moschoi, Giulia Biondani, Jean-François Peyron
The bone marrow microenvironment (BMME) is a complex ecosystem that instructs and protects hematopoietic stem cells (HSCs) and their malignant counterparts, the leukemia-initiating cells (LICs). Within the physical and functional crosstalk that takes place between HSCs, LICs, and the BMME, the transfer of organelles and of mitochondria in particular is an important new intercellular communication mode in addition to adhesion molecules, tunneling nanotubes (TNTs), and the paracrine secretion of cytokines, (onco)metabolites, and extracellular vesicles (EVs)...
December 2017: Trends in Cancer
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