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Salting the Soil: Targeting the Microenvironment of Brain Metastases.

Publication ,  Journal Article
Srinivasan, ES; Tan, AC; Anders, CK; Pendergast, AM; Sipkins, DA; Ashley, DM; Fecci, PE; Khasraw, M
Published in: Mol Cancer Ther
March 2021

Paget's "seed and soil" hypothesis of metastatic spread has acted as a foundation of the field for over a century, with continued evolution as mechanisms of the process have been elucidated. The central nervous system (CNS) presents a unique soil through this lens, relatively isolated from peripheral circulation and immune surveillance with distinct cellular and structural composition. Research in primary and metastatic brain tumors has demonstrated that this tumor microenvironment (TME) plays an essential role in the growth of CNS tumors. In each case, the cancerous cells develop complex and bidirectional relationships that reorganize the local TME and reprogram the CNS cells, including endothelial cells, pericytes, astrocytes, microglia, infiltrating monocytes, and lymphocytes. These interactions create a structurally and immunologically permissive TME with malignant processes promoting positive feedback loops and systemic consequences. Strategies to interrupt interactions with the native CNS components, on "salting the soil," to create an inhospitable environment are promising in the preclinical setting. This review aims to examine the general and specific pathways thus far investigated in brain metastases and related work in glioma to identify targetable mechanisms that may have general application across the spectrum of intracranial tumors.

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Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

March 2021

Volume

20

Issue

3

Start / End Page

455 / 466

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Humans
  • Brain Neoplasms
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1112 Oncology and Carcinogenesis
 

Citation

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Srinivasan, E. S., Tan, A. C., Anders, C. K., Pendergast, A. M., Sipkins, D. A., Ashley, D. M., … Khasraw, M. (2021). Salting the Soil: Targeting the Microenvironment of Brain Metastases. Mol Cancer Ther, 20(3), 455–466. https://doi.org/10.1158/1535-7163.MCT-20-0579
Srinivasan, Ethan S., Aaron C. Tan, Carey K. Anders, Ann Marie Pendergast, Dorothy A. Sipkins, David M. Ashley, Peter E. Fecci, and Mustafa Khasraw. “Salting the Soil: Targeting the Microenvironment of Brain Metastases.Mol Cancer Ther 20, no. 3 (March 2021): 455–66. https://doi.org/10.1158/1535-7163.MCT-20-0579.
Srinivasan ES, Tan AC, Anders CK, Pendergast AM, Sipkins DA, Ashley DM, et al. Salting the Soil: Targeting the Microenvironment of Brain Metastases. Mol Cancer Ther. 2021 Mar;20(3):455–66.
Srinivasan, Ethan S., et al. “Salting the Soil: Targeting the Microenvironment of Brain Metastases.Mol Cancer Ther, vol. 20, no. 3, Mar. 2021, pp. 455–66. Pubmed, doi:10.1158/1535-7163.MCT-20-0579.
Srinivasan ES, Tan AC, Anders CK, Pendergast AM, Sipkins DA, Ashley DM, Fecci PE, Khasraw M. Salting the Soil: Targeting the Microenvironment of Brain Metastases. Mol Cancer Ther. 2021 Mar;20(3):455–466.

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

March 2021

Volume

20

Issue

3

Start / End Page

455 / 466

Location

United States

Related Subject Headings

  • Tumor Microenvironment
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Humans
  • Brain Neoplasms
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 1112 Oncology and Carcinogenesis