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Can we determine why some tumors evolve to aggressive malignancy after years of indolence?

Background: Indolent tumors have been detected in a wide range of tumor sites. Very little is known about why these tumors persist for extended periods of time and then evolve to malignancy. Some are recognized as indolent after treatment, while others appear as a stage of natural tumor development before treatment. Still others are seen only at autopsy. Research to characterize these various tumors could help to understand what controls this state. Is it a true proliferatively dormant state or an active state that just balances cell division and death? How is this state maintained? Do tumors of the same site undergo similar transitions as they move from dormancy to malignancy? Can we predict which tumors will remain dormant and which one will progress?

Feasibility: Many of the tools for tumor profiling will be useful to help characterize these tumors. Modern molecular and cellular techniques can be used to help understand which pathways are active and essential in indolent states.

Implications of success: Expanded insight into the mechanisms that control tumor development promises to enrich our understanding of the cancer process. Characterization of indolent tumors will help us understand the mechanisms that hold tumor progression in check. Indolent tumors seldom pose any inherent risk to patients, so approaches that would hold other tumors in this state or that would extend the time that indolence persists could provide important therapeutic benefits.

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