Brain Metastasis: A Literary Review of the Possible Relationship Between Hypoxia and Angiogenesis in the Growth of Metastatic Brain Tumors

Abstract

Brain metastases are a common and deadly complication of many primary tumors. The progression of these tumors is poorly understood, and treatment options are limited. Two important components of tumor growth are hypoxia and angiogenesis. We conducted a review to look at the possibility of a symbiotic relationship between two transcription factors, Hypoxia-Inducible Factor 1α (HIF1α) and Vascular Endothelial Growth Factor (VEGF), and the role they play in metastasis to the brain. We delve further into this possible relationship by examining commonly used chemotherapeutic agents and their targets. Through an extensive literature review, we identified articles that provided evidence of a strong connection between these transcription factors and the growth of brain metastases, many highlighting a symbiotic relationship. Further supporting this, combinations of chemotherapeutic drugs with varying targets have increased the efficacy of treatment. Angiogenesis and hypoxia have long been known to play a large role in the invasion, growth, and poor outcomes of tumors. However, it is not fully understood how these factors influence one another during metastases. While prior studies have investigated the effects separately, we specifically delve into the synergistic and compounding effects that may exist between them. Our findings underscore the need for greater research allocation to investigate the possible symbiotic relationship between angiogenesis and hypoxia in brain metastasis.

Keywords: HIF1α; VEGF; angiogenesis; brain metastasis; hypoxia.

Figure 1

Four steps of tumor metastasis. (1) Tumor metastasis takes root in a blood vessel. (2) Tumor invades the tissue surrounding a vessel. (3) The tumor grows rapidly. (4) Co-opted vessels change in size and shape and begin forming new vasculature via angiogenesis.

Figure 2

When tumor cells grow past their original confines, they become hypoxic and trigger the activation of HIF1α, leading to the angiogenic switch that allows for the continued growth of blood vessels and the delivery of oxygen and nutrients to the tumor.