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open access
Redefining the origin and evolution of ovarian cancer: A hormonal connection
July 20, 2015
(pdf) Accepted Preprint first posted on 20 July 2016 as Manuscript ERC-16-0209
Abstract
Ovarian cancer has the highest
mortality of all female reproductive cancers. Late diagnosis, tumor
heterogeneity, and the
development of chemoresistance contribute to
this statistic and works against patient survival. Current studies have
revealed
novel concepts that impact our view on how
ovarian cancer develops. The greatest impact is on our understanding
that as a
disease, ovarian cancer has multiple cellular
origins and that these malignant precursors are mostly derived from
outside
of the ovaries.
In this review, we propose a new
concept of a step-wise developmental process that may underwrite ovarian
tumorigenesis and
progression: (1) migration to/recruitment of the
ovaries; (2) seeding and establishment in the ovaries; (3) induction of
a
dormant cancer stage; and (4) expansion and
tumor progression. We will discuss the relationship of each step with
the changing
ovarian function and milieu during the
reproductive age and subsequent occurrence of menopause. The
realization that ovarian
cancer development and progression occurs in
distinct steps is critical for the search of adequate markers for early
detection
that will offer personalized strategies for
prevention and therapy.
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