<![CDATA[Objective: To review the two designated pathways of ovarian
cancer and their implications to the management of ovarian cancer.
Method: Literature review
Result: A proposed carcinogenesis of ovarian cancer has been
developed based on a long history of pathological and molecular
genetic findings. It divides ovarian cancer as having designated type
I or type II pathway. Type I pathway involves ovarian carcinomas
with low-grade serous subtype, mucinous, clear cell and endometrioid
subtypes. They grow in a stepwise manner, shows low response
toward platinum-based chemotherapy and mostly relate to
MAPK pathway mutations. High-grade serous ovarian carcinomas
which are often found in rapid-aggressive progression with poorer
prognosis are suggested as type II pathway. Their major mutations
are mainly in TP53. Optimal surgery and adjuvant chemotherapy
are the treatment for both confined and advanced cancers. However,
the optimal cytoreduction in type II pathway is becoming more
important to increase overall survival or disease-free interval. The
strategy of screening type II pathway is proposed to be shifted from
detection of stage I tumors to detection of minimal ovarian carcinomas
probably by biomarkers since the rapid inception is hardly
found. Meanwhile the BRCA1/2 screening and classification should
be improved for the hereditary breast/ovarian cancer screening.
Mutations of KRAS, BRAF, PTEN and CTNNB1 occur majorly in
the type I tumors. Therefore, targeted chemotherapy and inhibitor
treatments which are investigated foremost in type II recurrence of
ovarian malignancies may also be directed to the low response of
type I pathway to platinum-based chemotherapy.
Conclusion: A different strategy based on the tumorigenesis of
ovarian cancer should be considered in term of screening, primary
approach and following chemotherapy since there are some distinctive
patterns in both pathways.
[Indones J Obstet Gynecol 2009;33-4:239-46]
Keywords: ovarian cancer, carcinogenesis, screening, cytoreduction,
chemotherapy]]>
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