Abstract
The tumor microenvironment is a key factor in disease progression, local resistance, immune-escaping, and metastasis. The rapid proliferation of tumor cells and the aberrant structure of the blood vessels within tumors result in a marked heterogeneity in the perfusion of the tumor tissue with regions of hypoxia. Although most of the tumor cells die in these hypoxic conditions, a part of them can adapt and survive for many days or months in a dormant state. Dormant tumor cells are characterized by cell cycle arrest in G0/G1 phase as well as a low metabolism, and are refractive to common chemotherapy, giving rise to metastasis. Despite these features, the cells retain their ability to proliferate when conditions improve. An understanding of the regulatory machinery of tumor dormancy is essential for identifying early cancer biomarkers and could provide a rationale for the development of novel agents to target dormant tumor cell populations. In this review, we examine the current knowledge of the mechanisms allowing tumor dormancy and discuss the crucial role of the hypoxic microenvironment in this process.
Highlights
The tumor mass is composed by cancer cells and by a variety of resident and infiltrating host cells, secreted factors and extracellular matrix components, known as the tumor microenvironment (TME)
Tumor progression is influenced by interactions of cancer cells with their environment that determine if the primary tumor is eradicated, metastasizes, or establishes dormant micro-metastases
Hypoxic signaling is mainly mediated via the hypoxia-inducible transcription factors (HIFs), that induce genes involved in angiogenesis, growth and cell survival, energy metabolism, invasion and metastasis
Summary
The tumor mass is composed by cancer cells and by a variety of resident and infiltrating host cells, secreted factors and extracellular matrix components, known as the tumor microenvironment (TME). Tumor progression is influenced by interactions of cancer cells with their environment that determine if the primary tumor is eradicated, metastasizes, or establishes dormant micro-metastases. The TME can influence therapeutic responses, justifying the recent research studies on new therapeutic approaches that target components of the TME
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