New clinical and experimental approaches for studying tumor dormancy: does tumor dormancy offer a therapeutic target?

Abstract

Goss P, Allan AL, Rodenhiser DI, Foster PJ, Chambers AF. New clinical and experimental approaches for studying tumor dormancy: does tumor dormancy offer a therapeutic target ? APMIS 2008;116:552-68. Tumor dormancy is a significant clinical problem. Primary treatment of a cancer may be apparently successful, and yet the tumor may recur either locally or as distant metastases years or even decades later. The ability to predict which patients are likely to develop recurrences is imprecise, relying on probabilities of recurrence based on features of the primary cancer. This uncertainty presents clinical challenges regarding who to treat and how, in order to prevent recurrence after periods of dormancy. Recent clinical trials in breast cancer support the idea that some patients may harbor tumor cells that are capable of forming late-developing metastases years after removal of the primary tumor, and that these dormant cancer cells may in some cases be effectively treated with long-term therapy. Advances in experimental studies of tumor dormancy are shedding light on the nature of dormancy, and are providing both new technologies and conceptual approaches for studying tumor dormancy. A better understanding of mechanisms responsible for tumor dormancy and recurrence will be important for improving care of patients at risk for late-developing metastases.

Dormant Cells: The Original Cause of Tumor Recurrence and Metastasis

“…It is still debatable if CSCs differ from dormant tumor cells. CSCs are defined as dormant cells due to their low proliferation rate, ability to exclude intracellular toxins, and resistance to chemotherapy and radiotherapy, which is very close to the definition of dormant cells [27,28]. Since stem cells are able to repopulate a whole system and self-renew, it could be argued that although dormant cells can repopulate a system, they will not be considered as stem cells unless they can self-renew [29].…”

P-cadherin signals through the laminin receptor α6β4 integrin to induce stem cell and invasive properties in basal-like breast cancer cells

“…Alterations in the ECM or in the integrin expression are implicated in the initiation and progression of breast cancer [13, 14]. For example, ECM remodeling and integrin activation assist in the malignant transformation of cells in the primary site, as well as in the activation of quiescent cells in distant metastatic sites, such as the bone, liver, lung and brain [15-18].…”

Framework models of tumor dormancy from patient-derived observations

“…The current knowledge about dormancy mechanisms has been reviewed in detail repeatedly [37][38][39][40][41] and therefore the task here is to categorize the principles underlying the non-productive state of DTCs.…”