Therapeutic Targeting of the Tumor Microenvironment

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 933 - 959

Published: April 1, 2021

Abstract Strategies to therapeutically target the tumor microenvironment (TME) have emerged as a promising approach for cancer treatment in recent years due critical roles of TME regulating progression and modulating response standard-of-care therapies. Here, we summarize current knowledge regarding most advanced TME-directed therapies, which either been clinically approved or are currently being evaluated trials, including immunotherapies, antiangiogenic drugs, treatments directed against cancer-associated fibroblasts extracellular matrix. We also discuss some challenges associated with future perspectives this evolving field. Significance: This review provides comprehensive analysis therapies targeting TME, combining discussion underlying basic biology clinical evaluation different therapeutic approaches, highlighting perspectives.

Language: Английский

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Next-generation cancer organoids

Nature Materials, Journal Year: 2021, Volume and Issue: 21(2), P. 143 - 159

Published: Aug. 12, 2021

Language: Английский

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Extracellular fluid viscosity enhances cell migration and cancer dissemination

Nature, Journal Year: 2022, Volume and Issue: 611(7935), P. 365 - 373

Published: Nov. 2, 2022

Abstract Cells respond to physical stimuli, such as stiffness 1 , fluid shear stress 2 and hydraulic pressure 3,4 . Extracellular viscosity is a key cue that varies under physiological pathological conditions, cancer 5 However, its influence on biology the mechanism by which cells sense changes in are unknown. Here we demonstrate elevated counterintuitively increases motility of various cell types two-dimensional surfaces confinement, dissemination from three-dimensional tumour spheroids. Increased mechanical loading imposed induces an actin-related protein 2/3 (ARP2/3)-complex-dependent dense actin network, enhances Na + /H exchanger (NHE1) polarization through actin-binding partner ezrin. NHE1 promotes swelling increased membrane tension, which, turn, activates transient receptor potential cation vanilloid 4 (TRPV4) mediates calcium influx, leading RHOA-dependent contractility. The coordinated action remodelling/dynamics, NHE1-mediated RHOA-based contractility facilitates enhanced at viscosities. Breast pre-exposed acquire TRPV4-dependent memory transcriptional control Hippo pathway, migration zebrafish, extravasation chick embryos lung colonization mice. Cumulatively, extracellular regulates both short- long-term cellular processes with pathophysiological relevance biology.

Language: Английский

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Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: May 24, 2021

Biophysical cues, such as mechanical properties, play a critical role in tissue growth and homeostasis. During organ development injury repair, compressive tensional forces generated by cell-extracellular matrix or cell-cell interaction are key factors for cell fate determination. In the vascular system, hemodynamic forces, shear stress, cyclic stretch modulate phenotypes susceptibility to atherosclerosis. Despite that emerging efforts have been made investigate how mechanotransduction is involved tuning functions various contexts, regulatory mechanisms remain largely unknown. One of challenges understand signaling cascades transmit cues from plasma membrane cytoplasm then nuclei generate mechanoresponsive transcriptomes. YAP its homolog TAZ, Hippo pathway effectors, identified mechanotransducers sense stimuli relay signals control transcriptional programs proliferation, differentiation, transformation. However, upstream mechanosensors YAP/TAZ downstream transcriptome responses following activation repression not well characterized. Moreover, mechanoregulation literature highly context-dependent. this review, we summarize biomechanical microenvironment provide an update on roles physiological pathological conditions.

Language: Английский

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Mechanical communication in fibrosis progression

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 32(1), P. 70 - 90

Published: Nov. 19, 2021

Language: Английский

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Engineered strategies to enhance tumor penetration of drug-loaded nanoparticles

Journal of Controlled Release, Journal Year: 2021, Volume and Issue: 341, P. 227 - 246

Published: Nov. 22, 2021

Language: Английский

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Towards principled design of cancer nanomedicine to accelerate clinical translation

Materials Today Bio, Journal Year: 2022, Volume and Issue: 13, P. 100208 - 100208

Published: Jan. 1, 2022

Nanotechnology in medical applications, especially oncology as drug delivery systems, has recently shown promising results. However, although these advances have been the pre-clinical stages, clinical translation of this technology is challenging. To create systems with increased treatment efficacy for translation, physicochemical characteristics nanoparticles such size, shape, elasticity (flexibility/rigidity), surface chemistry, and charge can be specified to optimize efficiency a given application. Consequently, interdisciplinary researchers focused on producing biocompatible materials, production technologies, or new formulations efficient loading, high stability. The effects design parameters studied

Language: Английский

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Context-Specific Determinants of the Immunosuppressive Tumor Microenvironment in Pancreatic Cancer

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(2), P. 278 - 297

Published: Jan. 9, 2023

Immunotherapies have shown benefits across a range of human cancers, but not pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that the immunosuppressive tumor microenvironment (TME) constitutes an important roadblock to their efficacy. The landscape TME differs substantially PDAC subtypes, indicating context-specific principles immunosuppression. In this review, we discuss how cells, local TME, and systemic host environmental factors drive immunosuppression in context. We argue unraveling mechanistic drivers modes will open new possibilities target more efficiently by using multimodal (immuno)therapeutic interventions. Immunosuppression is almost universal hallmark cancer, although entity highly heterogeneous its different subtypes phenotypes. Here, provide diverse cancer central executor various context-dependent immunosuppression, key challenges novel opportunities uncover, functionalize, functional nodes for therapeutic exploitation.

Language: Английский

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An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment

Cancers, Journal Year: 2022, Volume and Issue: 14(12), P. 2868 - 2868

Published: June 10, 2022

The enhanced permeability and retention (EPR) effect in cancer treatment is one of the key mechanisms that enables drug accumulation at tumor site. However, despite a plethora virus/inorganic/organic-based nanocarriers designed to rely on EPR effectively target tumors, most have failed clinic. It seems non-compliance research activities with clinical trials, goals unrelated effect, lack awareness impact solid structure interactions performance intensified this dissatisfaction. As such, asymmetric growth structural complexity physicochemical properties nanocarriers, analytical combination tools, description should be considered improve EPR-based therapeutics. This review provides valuable insights into limitations therapeutic efficacy reports crucial perspectives how can modulated effects nanomedicine.

Language: Английский

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Lymphatic vessels in cancer

Physiological Reviews, Journal Year: 2022, Volume and Issue: 102(4), P. 1837 - 1879

Published: June 30, 2022

The lymphatic system, composed of initial and collecting vessels as well lymph nodes that are present in almost every tissue the human body, acts an essential transport system for fluids, biomolecules, cells between peripheral tissues central circulation. Consequently, it is required normal body physiology but also involved pathogenesis various diseases, most notably cancer. important role tumor-associated lymphangiogenesis formation node metastasis has been elucidated during last two decades, whereas underlying mechanisms relation organ dissemination cancer incompletely understood. Lymphatic tumor-host communication, relaying molecular information from a primary or metastatic tumor to regional circulatory system. Beyond antigen transport, endothelial cells, particularly those residing sinuses, have recently recognized direct regulators immunity immunotherapy responsiveness, presenting antigens expressing several immune-modulatory signals including PD-L1. In this review, we summarize recent discoveries rapidly evolving field highlight strategies challenges therapeutic targeting specific functions patients.

Language: Английский

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