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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The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease

Cell, Journal Year: 2020, Volume and Issue: 182(2), P. 270 - 296

Published: July 1, 2020

Language: Английский

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Functional characterization of the dural sinuses as a neuroimmune interface

Cell, Journal Year: 2021, Volume and Issue: 184(4), P. 1000 - 1016.e27

Published: Jan. 27, 2021

Language: Английский

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Fluid transport in the brain

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 1025 - 1151

Published: May 5, 2021

The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. blood-brain barrier establishes stable environment that optimal for neuronal function, yet imposes physiological problem; transcapillary filtration forms extracellular fluid in other organs reduced to minimum brain. Consequently, depends on special [the cerebrospinal (CSF)] flushed into along perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined term glymphatic system, based dependency endfeet their adluminal expression of aquaporin-4 water channels facing CSF-filled spaces. Glymphatic clearance potentially harmful metabolic or protein waste products, such as amyloid-β, primarily active sleep, when drivers, cardiac cycle, respiration, slow vasomotion, together efficiently propel CSF inflow periarterial brain's space contains an abundance proteoglycans hyaluronan, which provide low-resistance hydraulic conduit rapidly can expand shrink sleep-wake cycle. system brain, meets requisites maintain homeostasis similar peripheral organs, considering blood-brain-barrier paths formation egress CSF.

Language: Английский

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Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics

Cellular and Molecular Life Sciences, Journal Year: 2021, Volume and Issue: 78(6), P. 2429 - 2457

Published: Jan. 11, 2021

Abstract Cerebrospinal fluid (CSF) is produced by the choroid plexuses within ventricles of brain and circulates through subarachnoid space skull spinal column to provide buoyancy maintain homeostasis cord. The question how CSF drains from has long puzzled scientists clinicians. For many decades, it was believed that arachnoid villi or granulations, outcroppings tissue project into dural venous sinuses, served as major outflow route. However, this concept been increasingly challenged in recent years, physiological imaging evidence several species accumulated showing tracers injected can instead be found lymphatic vessels draining cranium spine. With high-profile rediscovery meningeal located dura mater, another debate emerged regarding exact anatomical pathway(s) for reach system, with one side favoring direct efflux advocating pathways along exiting cranial nerves. In review, a summary historical contemporary different will presented, allowing reader gain further perspective on advances field. An improved understanding fundamental process may lead novel therapeutic approaches wide range neurological conditions, including hydrocephalus, neurodegeneration multiple sclerosis.

Language: Английский

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Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Sept. 10, 2020

Abstract Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model TBI that mild forms trauma severe deficits meningeal lymphatic drainage begin within hours last out to at least one month post-injury. To investigate mechanism underlying impaired function TBI, examined how increased intracranial pressure (ICP) influences the lymphatics. We ICP can contribute dysfunction. Moreover, show pre-existing dysfunction before leads neuroinflammation negative cognitive outcomes. Finally, report rejuvenation aged mice ameliorate TBI-induced gliosis. These findings provide insights into both causes consequences suggest therapeutics targeting system may offer strategies treat TBI.

Language: Английский

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Immunostimulant hydrogel for the inhibition of malignant glioma relapse post-resection

Nature Nanotechnology, Journal Year: 2021, Volume and Issue: 16(5), P. 538 - 548

Published: Feb. 1, 2021

Language: Английский

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Pathological angiogenesis: mechanisms and therapeutic strategies

Angiogenesis, Journal Year: 2023, Volume and Issue: 26(3), P. 313 - 347

Published: April 15, 2023

In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, coalescent well vessel co-option, vasculogenic mimicry lymphangiogenesis, underlie vasculature. many pathological conditions, cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but often done so without normal feedback that regulate ordinary spatial temporal patterns formation. Thus, angiogenesis presents challenges yet opportunities design vascular-directed therapies. Here, we provide overview recent insights into development highlight novel therapeutic strategies promote or inhibit to stabilize, reverse, even halt disease progression. our review, will also explore several additional aspects (the switch, hypoxia, angiocrine signals, endothelial plasticity, normalization, cell anergy) operate in parallel canonical speculate how these may be targeted with anti-angiogenic

Language: Английский

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Tumor-draining lymph nodes: At the crossroads of metastasis and immunity

Science Immunology, Journal Year: 2021, Volume and Issue: 6(63)

Published: Sept. 3, 2021

Early engagement of the lymphatic system by solid tumors in peripheral, nonlymphoid tissues is a clinical hallmark cancer and often forecasts poor prognosis. The significance lymph node metastasis for distant spread, however, has been questioned large-scale dissection trials likely prevalence direct hematogenous metastasis. Still, an emerging appreciation immunological role tumor-draining renewed interest its basic biology, metastatic progression, antitumor immunity, patient outcomes. In this review, we discuss our current understanding early mechanisms through which engage transport condition nodes, these changes both potential implications immunotherapy.

Language: Английский

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Challenges in glioblastoma research: focus on the tumor microenvironment

Trends in cancer, Journal Year: 2022, Volume and Issue: 9(1), P. 9 - 27

Published: Nov. 16, 2022

Language: Английский

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