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Metastatic tumor dormancy in cutaneous melanoma: does surgery induce escape?

Tseng WW, Fadaki N, Leong SP - Cancers (Basel) (2011)

Bottom Line: 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.Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, Room S-321, San Francisco, CA 94143, USA. leongsx@cpmcri.org.

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.

No MeSH data available.


Related in: MedlinePlus

Impaired angiogenesis (red vessels with dotted X) and immune regulation (T, NK cell) are the two major proposed mechanisms for maintenance of tumor dormancy. The net result is that single tumor cells (white) enter a state of cell cycle arrest (= G0, red) or there is a balance between the number of cells proliferating (green) and those undergoing apoptosis (gray with dotted X).
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f1-cancers-03-00730: Impaired angiogenesis (red vessels with dotted X) and immune regulation (T, NK cell) are the two major proposed mechanisms for maintenance of tumor dormancy. The net result is that single tumor cells (white) enter a state of cell cycle arrest (= G0, red) or there is a balance between the number of cells proliferating (green) and those undergoing apoptosis (gray with dotted X).

Mentions: Tumor dormancy is the concept that single cells or microscopic clusters of cells can remain viable but clinically undetectable for an extended period of time and still maintain the potential for malignant outgrowth [1-3]. Dormant tumor cells are thought to exist in a state of cell cycle arrest; alternatively, within clusters of tumor cells, an equilibrium is reached between cells undergoing proliferation and apoptosis or programmed cell death [1-3]. The experimental evidence to date, mostly from animal studies, suggests that tumor cells are kept in a dormant state by several mechanisms including impaired angiogenesis and immune regulation [4,5] (Figure 1). Under more favorable local microenvironmental conditions or through other, yet undefined stimuli, tumor cells can subsequently escape from dormancy to produce clinically detectable disease. Escape from tumor dormancy at metastatic sites may account for distant recurrence after supposed surgical “cure” of the primary tumor and therefore has tremendous clinical implication as an obstacle in the treatment of solid tumors.


Metastatic tumor dormancy in cutaneous melanoma: does surgery induce escape?

Tseng WW, Fadaki N, Leong SP - Cancers (Basel) (2011)

Impaired angiogenesis (red vessels with dotted X) and immune regulation (T, NK cell) are the two major proposed mechanisms for maintenance of tumor dormancy. The net result is that single tumor cells (white) enter a state of cell cycle arrest (= G0, red) or there is a balance between the number of cells proliferating (green) and those undergoing apoptosis (gray with dotted X).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756387&req=5

f1-cancers-03-00730: Impaired angiogenesis (red vessels with dotted X) and immune regulation (T, NK cell) are the two major proposed mechanisms for maintenance of tumor dormancy. The net result is that single tumor cells (white) enter a state of cell cycle arrest (= G0, red) or there is a balance between the number of cells proliferating (green) and those undergoing apoptosis (gray with dotted X).
Mentions: Tumor dormancy is the concept that single cells or microscopic clusters of cells can remain viable but clinically undetectable for an extended period of time and still maintain the potential for malignant outgrowth [1-3]. Dormant tumor cells are thought to exist in a state of cell cycle arrest; alternatively, within clusters of tumor cells, an equilibrium is reached between cells undergoing proliferation and apoptosis or programmed cell death [1-3]. The experimental evidence to date, mostly from animal studies, suggests that tumor cells are kept in a dormant state by several mechanisms including impaired angiogenesis and immune regulation [4,5] (Figure 1). Under more favorable local microenvironmental conditions or through other, yet undefined stimuli, tumor cells can subsequently escape from dormancy to produce clinically detectable disease. Escape from tumor dormancy at metastatic sites may account for distant recurrence after supposed surgical “cure” of the primary tumor and therefore has tremendous clinical implication as an obstacle in the treatment of solid tumors.

Bottom Line: 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.Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, Room S-321, San Francisco, CA 94143, USA. leongsx@cpmcri.org.

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.

No MeSH data available.


Related in: MedlinePlus