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Trends in Cancer

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https://www.readbyqxmd.com/read/28958390/learning-from-the-proteasome-how-to-fine-tune-cancer-immunotherapy
#1
REVIEW
Nathalie Vigneron, Joanna Abi Habib, Benoit J Van den Eynde
Cancer immunotherapy has recently emerged as a forefront strategy to fight cancer. Key players in antitumor responses are CD8(+) cytolytic T lymphocytes (CTLs) that can detect tumor cells that carry antigens, in other words, small peptides bound to surface major histocompatibility complex (MHC) class I molecules. The success and safety of cancer immunotherapy strategies depends on the nature of the antigens recognized by the targeted T cells, their strict tumor specificity, and whether tumors and antigen-presenting cells can efficiently process the peptide...
October 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28958389/jarid1-histone-demethylases-emerging-targets-in-cancer
#2
REVIEW
Kayla M Harmeyer, Nicole D Facompre, Meenhard Herlyn, Devraj Basu
JARID1 proteins are histone demethylases that both regulate normal cell fates during development and contribute to the epigenetic plasticity that underlies malignant transformation. This H3K4 demethylase family participates in multiple repressive transcriptional complexes at promoters and has broader regulatory effects on chromatin that remain ill-defined. There is growing understanding of the oncogenic and tumor suppressive functions of JARID1 proteins, which are contingent on cell context and the protein isoform...
October 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28958388/aberrant-dna-methylation-in-colorectal-cancer-what-should-we-target
#3
REVIEW
Janson W T Tse, Laura J Jenkins, Fiona Chionh, John M Mariadason
Colorectal cancers (CRCs) are characterized by global hypomethylation and promoter-specific DNA methylation. A subset of CRCs with extensive and co-ordinate patterns of promoter methylation has also been identified, termed the CpG-island methylator phenotype. Some genes methylated in CRC are established tumor suppressors; however, for the majority, direct roles in disease initiation or progression have not been established. Herein, we examine functional evidence of specific methylated genes contributing to CRC pathogenesis, focusing on components of commonly deregulated signaling pathways...
October 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28958387/kras-alleles-the-devil-is-in-the-detail
#4
REVIEW
Kevin M Haigis
KRAS is the most frequently mutated oncogene in cancer and KRAS mutation is commonly associated with poor prognosis and resistance to therapy. Since the KRAS oncoprotein is, as yet, not directly druggable, efforts to target KRAS mutant cancers focus on identifying vulnerabilities in downstream signaling pathways or in stress response pathways that are permissive for strong oncogenic signaling. One aspect of KRAS biology that is not well appreciated is the potential biological differences between the many distinct KRAS activating mutations...
October 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28958386/imaging-tunneling-membrane-tubes-elucidates-cell-communication-in-tumors
#5
REVIEW
Emil Lou, Sepideh Gholami, Yevgeniy Romin, Venugopal Thayanithy, Sho Fujisawa, Snider Desir, Clifford J Steer, Subbaya Subramanian, Yuman Fong, Katia Manova-Todorova, Malcolm A S Moore
Intercellular communication is a vital yet underdeveloped aspect of cancer pathobiology. This Opinion article reviews the importance and challenges of microscopic imaging of tunneling nanotubes (TNTs) in the complex tumor microenvironment. The use of advanced microscopy to characterize TNTs in vitro and ex vivo, and related extensions called tumor microtubes (TMs) reported in gliomas in vivo, has propelled this field forward. This topic is important because the identification of TNTs and TMs fills the gap in our knowledge of how cancer cells communicate at long range in vivo, inducing intratumor heterogeneity and resistance to treatment...
October 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28958385/engineering-tumor-hypersusceptibility-to-checkpoint-immunotherapy
#6
Ariel Fernández
The immune checkpoint blocker pembrolizumab (Keytruda) has proven successful in treating solid tumors harboring a DNA mismatch repair (MMR) deficiency. We show that it is possible to generate a drug-promoted phenotype mimicking the MMR deficiency in solid tumors, and thereby to engineer a generic hypersusceptibility to Keytruda through drug-induced metabolic stress on DNA synthesis. The potential of such drug-Keytruda combinations as universal treatments for solid tumors deserves clinical evaluation.
October 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28958384/all-paths-lead-to-trim25
#7
Hengbo Zhou, James C Costello
Identifying key factors that regulate the transition from primary to metastatic cancer is a fundamental challenge. Walsh et al. took a systems biology approach integrating computational, in vitro, and in vivo experiments to identify TRIM25 (tripartite motif containing 25) as a key factor that regulates metastatic gene signatures both at the transcriptional and post-transcriptional level in breast cancer. Targeting TRIM25 therapeutically is attractive because it governs a broad set of coordinated transcriptional modules that dictate metastatic progression...
October 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28867169/nitric-oxide-the-forgotten-child-of-tumor-metabolism
#8
REVIEW
Bahar Salimian Rizi, Abhinav Achreja, Deepak Nagrath
Nitric oxide (NO) is a signaling molecule with pleiotropic physiological roles in normal cells and pathophysiological roles in cancer. NO synthetase expression and NO synthesis are linked to altered metabolism, neoplasticity, invasiveness, chemoresistance, immune evasion, and ultimately to poor prognosis of cancer patients. Exogenous NO in the microenvironment facilitates paracrine signaling, mediates immune responses, and triggers angiogenesis. NO regulates posttranslational protein modifications, S-nitrosation, and genome-wide epigenetic modifications that can have both tumor-promoting and tumor-suppressing effects...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28867168/the-unfolded-protein-response-in-immunogenic-cell-death-and-cancer-immunotherapy
#9
REVIEW
Nicole Rufo, Abhishek D Garg, Patrizia Agostinis
The unfolded protein response (UPR) is a conserved pathway that is stimulated when endoplasmic reticulum (ER) proteostasis is disturbed or lost. Accumulating evidence indicates that chronic activation of the UPR supports the main hallmarks of cancer by favoring cancer cell-autonomous and nonautonomous processes, which ultimately foster the immunosuppressive and protumorigenic microenvironment. However, certain forms of therapy-induced ER stress can elicit immunogenic cancer cell death (ICD), which enables the release of key immunostimulatory or danger signals, eventually driving efficient antitumor immunity...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28867167/pediatric-acute-megakaryoblastic-leukemia-multitasking-fusion-proteins-and-oncogenic-cooperations
#10
REVIEW
Cécile K Lopez, Sébastien Malinge, Muriel Gaudry, Olivier A Bernard, Thomas Mercher
Pediatric leukemia presents specific clinical and genetic features from adult leukemia but the underpinning mechanisms of transformation are still unclear. Acute megakaryoblastic leukemia (AMKL) is the malignant accumulation of progenitors of the megakaryocyte lineage that normally produce blood platelets. AMKL is diagnosed de novo, in patients showing a poor prognosis, or in Down syndrome (DS) patients with a better prognosis. Recent data show that de novo AMKL is primarily associated with chromosomal alterations leading to the expression of fusions between transcriptional regulators...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28867166/targeting-inflammation-to-improve-tumor-drug-delivery
#11
REVIEW
Vasiliki Gkretsi, Lefteris C Zacharia, Triantafyllos Stylianopoulos
Inefficient delivery of drugs is a main cause of chemotherapy failure in hypoperfused tumors. To enhance perfusion and drug delivery in these tumors, two strategies have been developed: vascular normalization, aiming at normalizing tumor vasculature and blood vessel leakiness, and stress alleviation, aiming at decompressing tumor vessels. Vascular normalization is based on anti-angiogenic drugs, whereas stress alleviation is based on stroma-depleting agents. We present here an alternative approach to normalize tumor vasculature, taking into account that malignant tumors tend to develop at sites of chronic inflammation...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28867165/antitumor-antibodies-can-drive-therapeutic-t-cell-responses
#12
REVIEW
K Dane Wittrup
The classical view of therapeutic monoclonal antibodies (mAbs) against tumor-associated antigens (TAAs) is that their mechanism of action is dominated by signal blocking or the cytotoxicity of Fc-driven innate immune effector functions. We review here a mounting body of evidence that anti-TAA mAbs are capable of profoundly synergizing with T cell-directed immunotherapies such as checkpoint blockade and adoptive cell therapy. Two key components account for this synergy: (i) a self-vaccinal effect mediated by dendritic cells (DCs); and (ii) an inflammatory repolarization of the tumor microenvironment...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28867164/venom-peptides-improving-specificity-in-cancer-therapy
#13
Ravikiran Mahadevappa, Rui Ma, Hang Fai Kwok
Venom peptides (VPs) exhibit high specificity and selectivity towards cancer cells, with effects on cell proliferation, invasion, migration, and angiogenesis, as well as modulating immune responses. Studying VPs can help the design of more specific peptide drugs for targeted cancer therapy.
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780936/nad-deficits-in-age-related-diseases-and-cancer
#14
REVIEW
Amanda Garrido, Nabil Djouder
The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD(+) reduction as the central mechanism that may connect aging to its related pathologies and cancer...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780935/metabolic-regulation-of-tregs-in-cancer-opportunities-for-immunotherapy
#15
REVIEW
Haiping Wang, Fabien Franco, Ping-Chih Ho
The promising outcomes observed in cancer immunotherapy are evidence that the immune system provides a powerful arsenal for the restriction of tumor outgrowth; however, the immunosuppressive tumor microenvironment (TME) is known to impair antitumor immunity and impede the efficacy of cancer immunotherapies. Regulatory T cells (Tregs), which prevent overt immune responses and autoimmunity, accumulate aberrantly in some types of tumor to suppress antitumor immunity and support the establishment of an immunosuppressive microenvironment...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780934/sox4-joining-the-master-regulators-of-epithelial-to-mesenchymal-transition
#16
REVIEW
Ana Rita Lourenço, Paul J Coffer
The epithelial-to-mesenchymal transition (EMT) is an important developmental program exploited by cancer cells to gain mesenchymal features. Transcription factors globally regulating processes during EMT are often referred as 'master regulators' of EMT, and include members of the Snail and ZEB transcription factor families. The SRY-related HMG box (SOX) 4 transcription factor can promote tumorigenesis by endowing cells with migratory and invasive properties, stemness, and resistance to apoptosis, thereby regulating key aspects of the EMT program...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780933/%C3%AE-%C3%AE-t-cells-unexpected-regulators-of-cancer-development-and-progression
#17
REVIEW
Christopher Fleming, Samantha Morrissey, Yihua Cai, Jun Yan
Accumulating evidence suggests a role for gamma delta (γδ) T cells as unexpected drivers of tumor development and progression. These protumoral γδ T cells are abundant in the tumor microenvironment in both mouse and human. They promote tumor progression by: (i) inducing an immunosuppressive tumor microenvironment and angiogenesis via cytokine production; (ii) functioning as regulatory T (Treg)/T helper 2 (Th2)-like cells; (iii) interfering with dendritic cell (DC) effector function; and (iv) inhibiting antitumor adaptive T cell immunity via the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) pathway...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780932/cancer-nanomedicine-lessons-for-immuno-oncology
#18
REVIEW
Shiladitya Sengupta
Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades in the search for a cure for cancer. Exciting applications can emerge at the intersection of these two fields. However, it is important to learn from the past successes and failures of cancer nanomedicines for its future applications in cancer immunotherapy. This review discusses the two key parameters that defined clinical success in the case of cancer nanomedicines: (i) physicochemical design principles, and (ii) clinical trial design, which are frequently overlooked in most analyses of the state of the field...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780931/multiregional-tumor-trees-are-not-phylogenies
#19
João M Alves, Tamara Prieto, David Posada
Tumor samples most often comprise a mixture of different cell lineages. Multiregional trees built from bulk mutational profiles do not consider this heterogeneity and can potentially lead to erroneous evolutionary inferences, including biased timing of somatic mutations, spurious parallel mutation events, and/or incorrect chronological ordering of metastatic events.
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28780930/repurposing-drugs-in-oncology-next-steps
#20
Ciska Verbaanderd, Lydie Meheus, Isabelle Huys, Pan Pantziarka
The repurposing of existing non-cancer drugs is a potential source of new treatment options for cancer patients with high unmet medical needs. While scientific research is progressing rapidly in the field of drug repurposing, the implementation of drug repurposing still faces important financial and regulatory hurdles that should be addressed to optimise clinical adoption.
August 2017: Trends in Cancer
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