Targeting the Tumor Microenvironment in Brain Metastasis

Giridharan, Nisha; O’Brien, Barbara; Kerrigan, Brittany C. Parker; Heimberger, Amy B.; Ferguson, Sherise D.

doi:10.1016/j.nec.2020.06.011

Cited by 11 publications

(10 citation statements)

References 72 publications

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“…[105] Another clinical trial testing meclofenamate for recurrent/progressing BM is under way (NCT02429570). [106] In addition, since the efficiency of STAT3 inhibition has been demonstrated to suppress the growth of brain metastases in pre-clinical models, a clinical trial where 18 lung cancer patients suffering from BM are treated with Legasil (STAT3 inhibitor) has been performed. [107] Patients are administered with the inhibitor alone or in combination with other therapies.…”

Section: Anti-angiogenesis Therapiesmentioning

confidence: 99%

Tumor microenvironment in lung cancer-derived brain metastasis

Liu

Powell

Wang

2022

Chinese Medical Journal

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Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.

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Section: Anti-angiogenesis Therapiesmentioning

confidence: 99%

Tumor microenvironment in lung cancer-derived brain metastasis

Liu

Powell

Wang

2022

Chinese Medical Journal

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“…Diffusion-weighted imaging (DWI) has many advantages, being a quick, reproducible, and well-studied sequence in neuro-oncology, which is available on many standard scanners including in non-academic centers. In BM in particular, DWI parameters have been widely investigated as biomarkers of response to radiation and surgery ( 24 ) and may demonstrate biological change in both the tumor and the peritumoral region ( 25 , 26 ), the latter being especially important in immunotherapy response ( 5 ).…”

Section: Beyond Size and Shape: Perfusion And Diffusionmentioning

confidence: 99%

“…There is a clear clinical need for biomarkers that can predict the subsequent response to immunotherapy. The most logical way of doing this for ICI in BM would be demonstrating an immunologically favorable microenvironment before commencing treatment ( 4 , 5 ).…”

Section: Biomarkers To Predict Responsementioning

confidence: 99%

“…A number of trials of ICI for solid organ cancers that have included patients with BM suggest a heterogeneous but robust response in the brain [( 2 ) summary ( 3 ), for specific example in metastatic melanoma]. This has come on the background of increased investigation of the BM microenvironment and the understanding that this is an immunologically distinct rather than immune-isolated compartment ( 4 , 5 ). The immune response to BM therefore requires further investigation, to elucidate both the underlying mechanism of this response and that of resistance to therapeutics.…”

Section: Introductionmentioning

confidence: 99%

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The Role of the Immune Response in Brain Metastases: Novel Imaging Biomarkers for Immunotherapy

et al. 2021

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Brain metastases are a major clinical problem, and immunotherapy offers a novel treatment paradigm with the potential to synergize with existing focal therapies like surgery and radiosurgery or even replace them in future. The brain is a unique microenvironment structurally and immunologically. The immune response is likely to be crucial to the adaptation of systemic immune modulating agents against this disease. Imaging is frequently employed in the clinical diagnosis and management of brain metastasis, so it is logical that brain imaging techniques are investigated as a source of biomarkers of the immune response in these tumors. Current imaging techniques in clinical use include structural MRI (post-contrast T1W sequences, T2, and FLAIR), physiological sequences (perfusion- and diffusion-weighted imaging), and molecular imaging (MR spectroscopy and PET). These are reviewed for their application to predicting and measuring the response to immunotherapy in brain metastases.

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“…TME plays a critical regulatory role in the proliferation and invasion of tumor cells, especially in central nervous system metastases. The cellular and molecular mechanisms have been reported in several studies [7,8]. When leptomeningeal metastases happen, tumor cells in ltrate the BCSFB and circulate within the CSF.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive proteomic analysis of cerebrospinal fluid exosomes derived from non-small cell lung cancer related leptomeningeal carcinomatosis

Hou

Chen

et al. 2023

Preprint

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Background Leptomeningeal carcinomatosis might happen in late non-small cell lung cancer patients and causes a poor median survival period. CSF of leptomeningeal carcinomatosis patients is a special kind of tumor microenvironment. Exosomes are key components of tumor microenvironment and participate in a variety of physiological and pathological processes. There is a great need of comprehensive proteomic analysis of exosomes in these patients. Methods In this study, exosomes in CSF derived from different groups (leptomeningeal carcinomatosis group, non-small cell lung cancer group without leptomeningeal carcinomatosis and normal group) were isolated by ultracentrifugation and proteomics analysis was performed by label-free method. Results A total of 814 proteins were detected. Bioinformatics analysis revealed their shared function in the complement activation, extracellular region, and complement and coagulation cascades. 20 proteins were differentially expressed between groups. In protein-protein interaction network analysis, ACTB, ENO1, TIMP1 and RTN4R had higher betweenness than others. Conclusions This study is the first comprehensively CSF exosomes proteomic profile of leptomeningeal carcinomatosis patients. Further research is needed to clarify the importance of ACTB, ENO1, TIMP1 and RTN4R in leptomeningeal carcinomatosis patients.

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Targeting the Tumor Microenvironment in Brain Metastasis

Cited by 11 publications

References 72 publications

Tumor microenvironment in lung cancer-derived brain metastasis

Tumor microenvironment in lung cancer-derived brain metastasis

The Role of the Immune Response in Brain Metastases: Novel Imaging Biomarkers for Immunotherapy

Comprehensive proteomic analysis of cerebrospinal fluid exosomes derived from non-small cell lung cancer related leptomeningeal carcinomatosis

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