Awakening of Dormant Breast Cancer Cells in the Bone Marrow

Author:

Wieder Robert1ORCID

Affiliation:

1. Rutgers New Jersey Medical School and the Cancer Institute of New Jersey, 185 South Orange Avenue, MSB F671, Newark, NJ 07103, USA

Abstract

Up to 40% of patients with breast cancer (BC) have metastatic cells in the bone marrow (BM) at the initial diagnosis of localized disease. Despite definitive systemic adjuvant therapy, these cells survive in the BM microenvironment, enter a dormant state and recur stochastically for more than 20 years. Once they begin to proliferate, recurrent macrometastases are not curable, and patients generally succumb to their disease. Many potential mechanisms for initiating recurrence have been proposed, but no definitive predictive data have been generated. This manuscript reviews the proposed mechanisms that maintain BC cell dormancy in the BM microenvironment and discusses the data supporting specific mechanisms for recurrence. It addresses the well-described mechanisms of secretory senescence, inflammation, aging, adipogenic BM conversion, autophagy, systemic effects of trauma and surgery, sympathetic signaling, transient angiogenic bursts, hypercoagulable states, osteoclast activation, and epigenetic modifications of dormant cells. This review addresses proposed approaches for either eliminating micrometastases or maintaining a dormant state.

Funder

DOD

NIH

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference381 articles.

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