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Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape?
Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, Room S-321, San Francisco, CA 94143, USA
Department of Surgery and Center for Melanoma Research and Treatment, California Pacific Medical Center and Research Institute, 2340 Clay Street, 2nd floor, San Francisco, CA 94115, USA
* Author to whom correspondence should be addressed.
Received: 20 December 2010; in revised form: 28 January 2011 / Accepted: 11 February 2011 / Published: 21 February 2011
Abstract: According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed “cure” following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.
Keywords: tumor dormancy; cutaneous melanoma; metastasis; angiogenesis; adaptive immunity; surgery-induced growth; cancer stem cell; pre-metastatic niche
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Cite This Article
MDPI and ACS Style
Tseng, W.W.; Fadaki, N.; Leong, S.P. Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape? Cancers 2011, 3, 730-746.
Tseng WW, Fadaki N, Leong SP. Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape? Cancers. 2011; 3(1):730-746.
Tseng, William W.; Fadaki, Niloofar; Leong, Stanley P. 2011. "Metastatic Tumor Dormancy in Cutaneous Melanoma: Does Surgery Induce Escape?" Cancers 3, no. 1: 730-746.