When dormancy fuels tumour relapse

Abstract

Tumour recurrence is a serious impediment to cancer treatment, but the mechanisms involved are poorly understood. The most frequently used anti-tumour therapies—chemotherapy and radiotherapy—target highly proliferative cancer cells. However non- or slow-proliferative dormant cancer cells can persist after treatment, eventually causing tumour relapse. Whereas the reversible growth arrest mechanism allows quiescent cells to re-enter the cell cycle, senescent cells are largely thought to be irreversibly arrested, and may instead contribute to tumour growth and relapse through paracrine signalling mechanisms. Thus, due to the differences in their growth arrest mechanism, metabolic features, plasticity and adaptation to their respective tumour microenvironment, dormant-senescent and -quiescent cancer cells could have different but complementary roles in fuelling tumour growth. In this review article, we discuss the implication of dormant cancer cells in tumour relapse and the need to understand how quiescent and senescent cells, respectively, may play a part in this process.

Age Related Osteoporosis: Targeting Cellular Senescence

“…However, what distinguishes these states of cell cycle arrest is that quiescent cells can re-enter the cell cycle in response to appropriate mitogenic signals, whereas in senescent cells, the non-proliferative state in most cases is an irreversible one. An exception to this is seen in senescent tumor cells, which, given certain circumstances, are capable of resuming proliferative activity [ 21 , 22 , 23 , 24 , 25 ]. Another key feature distinguishing senescent form quiescent cells is halted proliferation combined with still ongoing cell growth.…”

Dormancy in Breast Cancer, the Role of Autophagy, lncRNAs, miRNAs and Exosomes

“…These cells may comprise two subpopulations; quiescent dormant tumour cells, which are also slow-cycling/slow-proliferating or stalled reversibly in the G0 phase of the cell cycle, and senescent dormant tumour cells that have irreversibly exited the cell cycle. The cell population intended throughout this review, however, encapsulates the quiescent dormant tumour cells described above, referred to herein as "dormant cells" that may not respond to therapy and subsequently lead to metastasis and disease recurrence [18][19][20][21][22][23][24]. In addition, the literature reports overlapping characteristics of cancer stem cells (CSCs) and quiescent dormant tumour cells, for instance, the ability to resist therapy, although in our opinion, cancer persister cells may be a better representative of the cell population resisting therapy, while CSCs may represent the cell population propagating an existing tumour [25].…”

Protocol for isolation and functional validation of label-retaining quiescent colorectal cancer stem cells from patient-derived organoids for RNA-seq

“…This is important since cells selectively surviving chemotherapy have been shown to be the same cells that are quiescent/slow cycling in untreated tumors and not cells that become quiescent upon treatment ( Francescangeli et al., 2020 ). Label retention strategies therefore enable the identification of long-term qCSCs with the potential to cause post-treatment disease relapse ( Dembinski and Krauss, 2009 ; Santos-de-Frutos and Djouder, 2021 ).…”