The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 20(1), P. 26 - 41

Published: Oct. 10, 2019

Language: Английский

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Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(4), P. 251 - 266

Published: Feb. 7, 2020

Language: Английский

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Angiogenic signaling pathways and anti-angiogenic therapy for cancer

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 11, 2023

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- anti-angiogenic molecules, which plays crucial role in tumor growth, invasion, metastasis. With advances molecular cellular biology, biomolecules such as growth factors, chemokines, adhesion factors involved angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules driven treatment to become promising strategy anti-tumor therapy. The most widely used agents include monoclonal antibodies tyrosine kinase inhibitors (TKIs) targeting vascular endothelial factor (VEGF) pathway. However, clinical benefit this modality still limited due several defects adverse events, acquired drug resistance, recurrence, lack validated biomarkers, impel further mechanisms angiogenesis, development multiple drugs combination therapy figure out how improve efficacy. Here, we broadly summarize signaling pathways discuss current challenges We also propose approaches efficacy provide perspective for

Language: Английский

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Turning cold tumors into hot tumors by improving T-cell infiltration

Theranostics, Journal Year: 2021, Volume and Issue: 11(11), P. 5365 - 5386

Published: Jan. 1, 2021

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on infiltration T cells capable recognizing and killing cells. ICIs are not effective in "cold tumors", which characterized lack T-cell infiltration. To realize full potential immunotherapy solve this obstacle, it is essential to understand drivers into tumors. We present a critical review our understanding mechanisms underlying including impaired priming deficient homing beds. "Hot tumors" with significant associated better ICI efficacy. In review, we summarize multiple strategies that promote transformation "hot discuss these lead increased Finally, application nanomaterials provide an outlook future emerging field. The combination nanomedicines enhances cross-presentation antigens promotes A deeper opens new possibilities for development cell-based therapies improve effectiveness.

Language: Английский

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Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability

eLife, Journal Year: 2019, Volume and Issue: 8

Published: April 16, 2019

Cancer cell metabolism is heavily influenced by microenvironmental factors, including nutrient availability. Therefore, knowledge of levels essential to understand tumor metabolism. To measure the extracellular available tumors, we utilized quantitative metabolomics methods absolute concentrations >118 metabolites in plasma and interstitial fluid, fluid that perfuses tumors. Comparison revealed nutrients tumors differ from those present circulation. Further, comparing between autochthonous transplant models murine pancreatic lung adenocarcinoma, found type, anatomical location animal diet affect local These data provide a comprehensive characterization microenvironment widely used cancer identify factors influence metabolite

Language: Английский

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Normalizing Function of Tumor Vessels: Progress, Opportunities, and Challenges

Annual Review of Physiology, Journal Year: 2019, Volume and Issue: 81(1), P. 505 - 534

Published: Feb. 10, 2019

Abnormal blood and lymphatic vessels create a hostile tumor microenvironment characterized by hypoxia, low pH, elevated interstitial fluid pressure. These abnormalities fuel progression, immunosuppression, treatment resistance. In 2001, we proposed novel hypothesis that the judicious use of antiangiogenesis agents—originally developed to starve tumors—could transiently normalize improve outcome anticancer drugs administered during window normalization. addition providing preclinical clinical evidence in support this hypothesis, also revealed underlying molecular mechanisms. parallel, demonstrated desmoplasia could impair vascular function compressing vessels, normalizing extracellular matrix both settings. Here, summarize progress made understanding applying normalization concept cancer outline opportunities challenges ahead patient outcomes using various strategies.

Language: Английский

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Combining Nanomedicine and Immunotherapy

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 52(6), P. 1543 - 1554

Published: May 23, 2019

ConspectusNanomedicine holds significant potential to improve the efficacy of cancer immunotherapy. Thus far, nanomedicines, i.e., 1–100(0) nm sized drug delivery systems, have been primarily used balance between and toxicity conjugated or entrapped chemotherapeutic drugs. The clinical performance nanomedicines has somewhat disappointing, which is arguably mostly due lack tools technologies for patient stratification. Conversely, progress made with immunotherapy spectacular, achieving complete cures inducing long-term survival in advanced-stage patients. Unfortunately, however, only works well relatively small subsets Increasing amounts preclinical data demonstrate that combining nanomedicine can boost therapeutic outcomes, by turning "cold" nonimmunoresponsive tumors metastases into "hot" immunoresponsive lesions.Nano-immunotherapy be realized via three different approaches, are (1) target cells, (2) tumor immune microenvironment, (3) peripheral system. When targeting typically aim induce immunogenic cell death, thereby triggering release antigens danger-associated molecular patterns, such as calreticulin translocation, high mobility group box 1 protein adenosine triphosphate. latter serve adjuvants alert antigen-presenting cells take up, process present former, promoting generation CD8+ cytotoxic T cells. Nanomedicines microenvironment potentiate inhibiting immunosuppressive M2-like tumor-associated macrophages, reducing expression molecules, transforming growth factor beta. In addition, employed promote activity microenvironment. system enhance antigen presentation production secondary lymphoid organs, lymph nodes spleen, engineer strengthen effector populations, anticancer immunity.While majority immunomodulatory development, exciting results already reported initial trials. To ensure efficient translation nano-immunotherapy constructs concepts, we consider biomarkers their make sure right formulation combined patient. this context, learn from currently ongoing efforts nano-biomarker identification partially established immuno-biomarker initiatives, Immunoscore immunogram. Together, these protocols will help capture nano-immuno status individual patients, enabling use individualized improved nanomedicine-based treatments

Language: Английский

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Targeting the gut and tumor microbiota in cancer

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 690 - 703

Published: April 1, 2022

Language: Английский

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Fluids and their mechanics in tumour transit: shaping metastasis

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 20(2), P. 107 - 124

Published: Nov. 28, 2019

Language: Английский

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Challenges of applying multicellular tumor spheroids in preclinical phase

Cancer Cell International, Journal Year: 2021, Volume and Issue: 21(1)

Published: March 4, 2021

Abstract The three-dimensional (3D) multicellular tumor spheroids (MCTs) model is becoming an essential tool in cancer research as it expresses intermediate complexity between 2D monolayer models and vivo solid tumors. MCTs closely resemble tumors many aspects, such the heterogeneous architecture, internal gradients of signaling factors, nutrients, oxygenation. have growth kinetics similar to those tumors, cells spheroid mimic physical interaction cell-to-cell cell-to-extracellular matrix interactions. These similarities provide great potential for studying biological properties a promising platform drug screening therapeutic efficacy evaluation. However, are not well adopted preclinical tools behavior up now. In this review, we addressed challenges with application discussed various efforts overcome challenges.

Language: Английский

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