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Figure 2. Synthetic summary of cellular and molecular events and interventions associated with dormancy. Cellular and molecular
events promoting entering into dormancy or escape from dormancy are listed based on their implication in the three forms of dormancy.
Classification is based on the main mechanisms and does not consider potential cross talk between different types of dormancy

cellular dormancy. Quiescent endothelial-derived thrombospondin-1 induces sustained quiescence of DTC in
breast cancer, while sprouting vessels wake dormant DTC and promote their outgrowth [122,184,185] [Figure 2].

DORMANT CANCER CELLS ARE RESISTANT TO THE CYTOTOXIC EFFECTS OF
CHEMOTHERAPY
Adjuvant chemotherapy significantly improves breast cancer patient survival, in particular for TNBC,
by decreasing the hazard of relapse after surgical removal of the primary tumor [26,32,186-188] . Relapses and
metastases however still occur in a fraction of patients and are likely due to tumor cells that had already
invaded the surrounding tissue, lymphatic vessels and lymph nodes, or disseminated through the blood
stream to the bone marrow and distant sites prior to surgery and resume grow at a later time point [60,77,189] . As
it is generally assumed that adjuvant chemotherapy acts by killing tumor cells, a corollary of this assumption
is that relapses are due to DTC resuming growth at a later time point after surviving chemotherapy.
Dormant, poorly proliferative DTC may not be affected by chemotherapy and may persist upon treatment
since chemotherapeutic drugs mainly target highly proliferating cells. This has been shown for instance in