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2012 RFA Links and Provocative Questions  

PQC - 6
What molecular events establish tumor dormancy after treatment and what leads to recurrence?

Background: Even apparently successful cancer therapy may leave dormant tumors or other types of minimal residual disease. These dormant tumors may remain stable for decades and in the best cases will not present further danger to the patient. However, frequently these tumors may undergo poorly understood changes and become aggressive and dangerous lesions. This Provocative Question seeks molecular explanations to both how these dormant tumors are generated and what might lead to their re-emergence as malignant tumors.

Feasibility: Perhaps the most difficult aspect of this question will be to identify a system where these dormant tumors can be studied in a reproducible manner. One can imagine that the use of mouse models may be possible or there may be types of human tumors treated under specific regimens that lead frequently to the appearance of dormant tumors. In these cases, it presumably will be the recurrent tumors arising from dormancy that will be available for careful study. These tumors could be profiled using modern biological methodologies to look for potential similarities or differences.

Implications of success: This is a stage of tumor development that has been difficult to study to date, and we, therefore, know very little about how these tumors arise or why malignant variants eventually arise. Advances in methods to characterize these unusual stages of tumors and the increasing knowledge of the primary tumors for comparison promise to allow the field to determine how these dormant tumors arise, how to look for these types of tumors after treatment, and which ones will be most important to follow.

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