Escape from Tumor Cell Dormancy
Annual rept. 22 Sep 2010-21 Sep 2011
MASSACHUSETTS INST OF TECH CAMBRIDGE
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An insidiously terrifying aspect of breast cancer is its propensity to recur in metastatic sites even over a decade after all evidence of cancer has passed. It is obvious that these cells had escaped very early from the primary tumor as this occurs even in small, nodenegative and in situ primary lesions, and that these micrometastases survival chemotherapeutic regimens that shrink and extirpate the primary carcinomas. Thus this mortal turn of events leads to three key questions how do the cells escape early, how do they survive over extended periods, and what causes these dormant lesions to become aggressive at these late dates The area of metastatic dissemination of primary cells has received a great level of inspection with an understanding of underlying molecular mechanisms, even if we do not yet have therapies. While chemotherapy survival in ectopic sites has been studies more recently, this is usually done in the context of a growing lesion. The truly under-appreciated and under-studied aspect is the last, that of reemergence from dormancy. Understanding what triggers dormant breast cancer cells to emerge and form frank and mortal metastases would allow the development not only of rationale therapeutics but of prevention and possibly lifestyle avoidance. Herein, these issues are addressed using a novel organotypic bioreactor in which tumor cells can be followed for weeks to months, the process of seeding, dormancy and emergence can be followed.
- Anatomy and Physiology
- Medicine and Medical Research