Immunity, Год журнала: 2020, Номер 54(1), С. 116 - 131.e10
Опубликована: Дек. 2, 2020
Язык: Английский
Nature Medicine, Год журнала: 2021, Номер 27(2), С. 212 - 224
Опубликована: Фев. 1, 2021
Язык: Английский
Процитировано
567
Advanced Drug Delivery Reviews, Год журнала: 2020, Номер 159, С. 245 - 293
Опубликована: Янв. 1, 2020
With the advent of effective tools to study lipids, including mass spectrometry-based lipidomics, lipids are emerging as central players in cancer biology. Lipids function essential building blocks for membranes, serve fuel drive energy-demanding processes and play a key role signaling molecules regulators numerous cellular functions. Not unexpectedly, cells, well other cell types tumor microenvironment, exploit various ways acquire extensively rewire their metabolism part plastic context-dependent metabolic reprogramming that is driven by both oncogenic environmental cues. The resulting changes fate composition help cells thrive changing microenvironment supporting functions hallmarks, energetics, promoting feedforward signaling, resisting oxidative stresses, regulating intercellular communication immune responses. Supported close connection between altered lipid pathogenic process, specific profiles unique disease biomarkers, with diagnostic, prognostic predictive potential. Multiple preclinical studies illustrate translational promise exploiting cancer, critically, have shown context dependent actionable vulnerabilities can be rationally targeted, particularly combinatorial approaches. Moreover, themselves used membrane disrupting agents or components nanocarriers therapeutics. number compounds strategies approaching clinical trials, we at doorstep hitherto underappreciated hallmark promising target oncologist's strategy combat cancer.
Язык: Английский
Процитировано
465
Cell, Год журнала: 2020, Номер 180(4), С. 729 - 748.e26
Опубликована: Фев. 1, 2020
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences perturbations to the p53 Wnt/β-catenin pathways, identified potential role for circRNAs in epithelial-mesenchymal transition, provided information about proteomic markers clinical genomic tumor subgroups, including relationships known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling histone acetylation. also characterized aspects immune landscape, immunogenic alterations, neoantigens, common cancer/testis antigens, microenvironment, all which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide valuable resource researchers clinicians, identify molecular associations mechanistic significance development cancers, suggest novel approaches identifying therapeutic targets.
Язык: Английский
Процитировано
383
Frontiers in Oncology, Год журнала: 2020, Номер 10
Опубликована: Авг. 6, 2020
Over the last decade, based on extensive development of preclinical animal studies and clinical trials, efficacy mechanisms immunotherapy have been fully explored. Significant lasting responses with provide a new breakthrough treatment for variety refractory cancer histologies, which gradually change pattern tumors. However, although ICI drugs are promising achieving longer term efficacy, their benefits in overall population still very low, such as low frequency response some common tumor types breast prostate, heterogeneity degree among different lesions same patient, making many limitations challenges. Most patients do not respond to or inevitably develop resistance after period treatment, manifesting primary acquired who initially treatment. The immune complex involve multiple aspects genes, metabolism, inflammation, abnormal neovascularization. Currently, characterized, more continue be uncovered. These efforts can improve quality medical care diagnosis life patients, finally lead accurate individualized This review discusses including tumor-intrinsic factors tumor-extrinsic factors.
Язык: Английский
Процитировано
261
Clinical Proteomics, Год журнала: 2020, Номер 17(1)
Опубликована: Май 24, 2020
Abstract Cancer biomarkers have transformed current practices in the oncology clinic. Continued discovery and validation are crucial for improving early diagnosis, risk stratification, monitoring patient response to treatment. Profiling of tumour genome transcriptome now established tools novel biomarkers, but alterations proteome expression more likely reflect changes pathophysiology. In past, clinical diagnostics strongly relied on antibody-based detection strategies, these methods carry certain limitations. Mass spectrometry (MS) is a powerful method that enables increasingly comprehensive insights into advance personalized medicine. this review, recent improvements MS-based proteomics highlighted with focus oncology. We will provide detailed overview clinically relevant samples types, as well as, consideration sample preparation methods, protein quantitation MS configurations, data analysis pipelines currently available researchers. Critical each step necessary address pressing questions cancer diagnosis prognosis. While majority studies clinically-relevant there growing demand rigorous biomarker validation. These high-throughput targeted assays multi-centre standardized protocols. Additionally, sensitivity opening door new classes tumour-specific proteoforms including post-translational modifications variants originating from genomic aberrations. Overlaying proteomic complement transcriptomic datasets forges field proteogenomics, which shows great potential improve our understanding biology. Overall, advancements not only solidify proteomics’ integral position research, also accelerate shift towards becoming regular component routine practice.
Язык: Английский
Процитировано
245
eLife, Год журнала: 2020, Номер 9
Опубликована: Май 5, 2020
Breakthroughs in anti-tumor immunity have led to unprecedented advances immunotherapy, yet it is now clear that the tumor microenvironment (TME) restrains immunity. T cells must substantially increase nutrient uptake mount a proper immune response and failure obtain sufficient nutrients or engage appropriate metabolic pathways can alter prevent effector cell differentiation function. The TME, however, be metabolically hostile due insufficient vascular exchange cancer metabolism leads hypoxia, depletion of nutrients, accumulation waste products. Further, inhibitory receptors present TME inhibit signaling both directly through release extracellular vesicles such as exosomes. This review will discuss changes drive into different stages their development how imposes barriers activity infiltrating lymphocytes.
Язык: Английский
Процитировано
239
Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)
Опубликована: Дек. 20, 2021
Abstract Melanoma is the most lethal skin cancer that originates from malignant transformation of melanocytes. Although melanoma has long been regarded as a cancerous malignancy with few therapeutic options, increased biological understanding and unprecedented innovations in therapies targeting mutated driver genes immune checkpoints have substantially improved prognosis patients. However, low response rate inevitable occurrence resistance to currently available targeted posed obstacle path management obtain further amelioration. Therefore, it necessary understand mechanisms underlying pathogenesis more comprehensively, which might lead substantial progress approaches expand clinical options for therapy. In this review, we firstly make brief introduction epidemiology, subtypes, risk factors, current therapies. Then, signal pathways orchestrating pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, pro-angiogenic systemically reviewed discussed. Subsequently, outline progresses checkpoints, well treatment resistance. Finally, prospects challenges development therapy, especially immunotherapy related ongoing trials, are summarized
Язык: Английский
Процитировано
225
MedComm, Год журнала: 2020, Номер 2(1), С. 27 - 59
Опубликована: Дек. 24, 2020
Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, source material for biogenesis of cell membranes. The enhanced synthesis, storage, uptake contribute to cancer progression. rewiring has been linked activation oncogenic pathways cross talk with tumor microenvironment. resulting activity favors survival proliferation cells harsh conditions within tumor. Lipid also plays a vital role immunogenicity via effects on function noncancer microenvironment, especially immune-associated cells. Targeting altered shown potential promising anticancer therapy. Here, we review recent evidence implicating contribution reprogramming progression, discuss molecular mechanisms underlying cancer, therapeutic strategies directed toward This sheds new light fully understanding context provides valuable clues targeting
Язык: Английский
Процитировано
215
Cancer Cell, Год журнала: 2021, Номер 39(9), С. 1190 - 1201
Опубликована: Авг. 19, 2021
Язык: Английский
Процитировано
215
Frontiers in Medicine, Год журнала: 2021, Номер 8
Опубликована: Сен. 22, 2021
Proteomics has become an important field in molecular sciences, as it provides valuable information on the identity, expression levels, and modification of proteins. For example, cancer proteomics unraveled key mechanistic studies tumor growth metastasis, which contributed to identification clinically applicable biomarkers well therapeutic targets. Several proteome databases have been established are being shared worldwide. Importantly, integration with other omics is providing extensive data related mechanisms target modulators. These may be analyzed processed through bioinformatic pipelines obtain useful information. The purpose this review provide overview recent advances proteomic techniques. In particular, we aim offer insights into current brain cancer, applications a relatively early stage. This covers from discovery characterization technology. Moreover, addresses global trends approaches for translational research. As core method research, continued development expected at scale beyond that previously seen.
Язык: Английский
Процитировано
184