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New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

ABSTRACT: The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress.

SUBMITTER: Boltze J

PROVIDER: S-EPMC7876251 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

Boltze Johannes J Aronowski Jaroslaw A JA Badaut Jerome J Buckwalter Marion S MS Caleo Mateo M Chopp Michael M Dave Kunjan R KR Didwischus Nadine N Dijkhuizen Rick M RM Doeppner Thorsten R TR Dreier Jens P JP Fouad Karim K Gelderblom Mathias M Gertz Karen K Golubczyk Dominika D Gregson Barbara A BA Hamel Edith E Hanley Daniel F DF Härtig Wolfgang W Hummel Friedhelm C FC Ikhsan Maulana M Janowski Miroslaw M Jolkkonen Jukka J Karuppagounder Saravanan S SS Keep Richard F RF Koerte Inga K IK Kokaia Zaal Z Li Peiying P Liu Fudong F Lizasoain Ignacio I Ludewig Peter P Metz Gerlinde A S GAS Montagne Axel A Obenaus Andre A Palumbo Alex A Pearl Monica M Perez-Pinzon Miguel M Planas Anna M AM Plesnila Nikolaus N Raval Ami P AP Rueger Maria A MA Sansing Lauren H LH Sohrabji Farida F Stagg Charlotte J CJ Stetler R Anne RA Stowe Ann M AM Sun Dandan D Taguchi Akihiko A Tanter Mickael M Vay Sabine U SU Vemuganti Raghu R Vivien Denis D Walczak Piotr P Wang Jian J Xiong Ye Y Zille Marietta M

Frontiers in aging neuroscience 20210128

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and ...[more]

PMID: 33584250

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Project description:Cancer immunotherapy, especially immune checkpoint blockade (ICB), has revolutionized oncology. However, only a limited number of patients benefit from immunotherapy, and some cancers that initially respond to immunotherapy can ultimately relapse and progress. Thus, some studies have investigated combining immunotherapy with other therapies to overcome resistance to monotherapy. Recently, multiple preclinical and clinical studies have shown that tumor vasculature is a determinant of whether immunotherapy will elicit an antitumor response; thus, vascular targeting may be a promising strategy to improve cancer immunotherapy outcomes. A successful antitumor immune response requires an intact "Cancer-Immunity Cycle," including T cell priming and activation, immune cell recruitment, and recognition and killing of cancer cells. Angiogenic inducers, especially vascular endothelial growth factor (VEGF), can interfere with activation, infiltration, and function of T cells, thus breaking the "Cancer-Immunity Cycle." Together with immunostimulation-regulated tumor vessel remodeling, VEGF-mediated immunosuppression provides a solid therapeutic rationale for combining immunotherapy with antiangiogenic agents to treat solid tumors. Following the successes of recent landmark phase III clinical trials, therapies combining immune checkpoint inhibitors (ICIs) with antiangiogenic agents have become first-line treatments for multiple solid tumors, whereas the efficacy of such combinations in other solid tumors remains to be validated in ongoing studies. In this review, we discussed synergies between antiangiogenic agents and cancer immunotherapy based on results from preclinical and translational studies. Then, we discussed recent progress in randomized clinical trials. ICI-containing combinations were the focus of this review because of their recent successes, but combinations containing other immunotherapies were also discussed. Finally, we attempted to define critical challenges in combining ICIs with antiangiogenic agents to promote coordination and stimulate collaboration within the research community.

Dataset Information

New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

Publications

New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

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