Acta Neuropathologica: Multigroup molecular maps reveal potential targeting abnormalities common to multiple histology of brain metastasis

Brain metastasis (BM) is a common and fatal complication of systemic malignancies, which often occurs in 10-30% of adult cancer patients.
The inherent limitations of surgical access and drug penetration within the central nervous system (CNS) further complicate the treatment of BM, and these limitations become more clinically relevant as the treatment of primary or other transcranial dispersal malignancies continues to improve.
BM is most commonly found in relatively narrow tumor cross-sections, including lung, breast and kidney cancers, and malignant melanomas, suggesting that common biological mechanisms play a fundamental role in common brain metastatic tumor types.
To identify and describe these mechanisms, the study used all-exon sequencing, mRN-seq, and introphic protein array analysis to perform genomic, transcriptional, and proteomic analysis of lung, breast and renal cell carcinomas, including BM and patient-matched primary or extracranial metastasis tissue.
Although no specific genomic changes were associated with BM, the correlation with cellular immunodeficiency, oxyphosphatation (OXPHOS) and typical carcinogenic signaling pathps, including inositol 3 kinase (PI3K) signals, was evident in a variety of tumor histology.
multiple immunofluorescence analysis confirmed significant T-cell depletion in BM, indicating a fundamental change in the immune micro-environment.
addition, functional studies using in vitro and in vivo models have shown that the oxidation metabolism in mouse BM models and brain metastasis derivatives is enhanced and sensitive to OXPHOS inhibition compared to the gene parent.
, pathophysiological recombination of carcinogenic signals, cell metabolism and immune microencienties is a widespread feature of BM.
further analysis of this biology could reveal promising targets for the development of treatments for BM caused by multiple systemic cancers.
Fukumura, K., Malgulwar, P.B., Fischer, G.M. et al. Multi-omic molecular profiling reveals potentially targetable abnormalities shared across multiple histologies of brain metastasis. Acta Neuropathol (2021). MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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