Tuning Cancer Fate: Tumor Microenvironment's Role in Cancer Stem Cell Quiescence and Reawakening.

Antonella Sistigu,Claudia Galassi,Ilio Vitale,Martina Musella,Ruggero De Maria

doi:10.3389/fimmu.2020.02166

Abstract

Cancer cell dormancy is a common feature of human tumors and represents a major clinical barrier to the long-term efficacy of anticancer therapies. Dormant cancer cells, either in primary tumors or disseminated in secondary organs, may reawaken and relapse into a more aggressive disease. The mechanisms underpinning dormancy entry and exit strongly resemble those governing cancer cell stemness and include intrinsic and contextual cues. Cellular and molecular components of the tumor microenvironment persistently interact with cancer cells. This dialog is highly dynamic, as it evolves over time and space, strongly cooperates with intrinsic cell nets, and governs cancer cell features (like quiescence and stemness) and fate (survival and outgrowth). Therefore, there is a need for deeper insight into the biology of dormant cancer (stem) cells and the mechanisms regulating the equilibrium quiescence-versus-proliferation are vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. Here, we review and discuss microenvironmental regulations of cancer dormancy and its parallels with cancer stemness, and offer insights into the therapeutic strategies adopted to prevent a lethal recurrence, by either eradicating resident dormant cancer (stem) cells or maintaining them in a dormant state.

Highlights

Despite the many noteworthy improvements in early diagnosis and treatment of primary tumors in recent years, in many cases, cancer patients develop distant metastases that, almost invariably, portend a poor prognosis
The current view is that metastatic relapse is caused by the reawakening of disseminated cancer cells (DCCs) from a dormant and asymptomatic state, after a time-lag lasting from a few months to several years
Cancer dormancy is considered a crucial part of the natural history of cancer evolution, irrespective of whether it occurs during primary tumor development or metastatic colonization [4] (Figure 1)

Summary

Introduction

Despite the many noteworthy improvements in early diagnosis and treatment of primary tumors in recent years, in many cases, cancer patients develop distant metastases that, almost invariably, portend a poor prognosis. This is supported by the evidence that cancer stem cells (CSCs)—the subset of cancer cells endowed with self-renewal ability, therapy-resistance, and immune evasion [8,9,10]—may switch between dormant and proliferative states [6, 7], resulting in an increased metastatic potential [11].

Results

Conclusion