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New perspectives on molecular targeted therapy in ovarian clear cell carcinoma.

ABSTRACT: Ovarian clear cell carcinomas (OCCCs) account for about 5-13% of all epithelial ovarian carcinomas in Western populations. It is characterised by resistance to conventional platinum-based chemotherapy, and new therapeutic strategies are urgently required. This article will focus on how recent discoveries have enhanced our understanding of the molecular pathogenesis of OCCCs, leading to new therapeutic opportunities. These include mutations in ARID1A, which provides a link to endometriosis, upregulation of the phosphatidylinositol 3-kinase/AKT pathway, particularly through mutations of PIK3CA and inactivation of PTEN, and increased activity of pathways involved in angiogenesis. Targeting HER2, apoptotic escape mechanisms and mismatch repair defects offer additional opportunities for treating this enigmatic tumour subtype.

SUBMITTER: Tan DS

PROVIDER: S-EPMC3668466 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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New perspectives on molecular targeted therapy in ovarian clear cell carcinoma.

Tan D S P DS Miller R E RE Kaye S B SB

British journal of cancer 20130404 8

Ovarian clear cell carcinomas (OCCCs) account for about 5-13% of all epithelial ovarian carcinomas in Western populations. It is characterised by resistance to conventional platinum-based chemotherapy, and new therapeutic strategies are urgently required. This article will focus on how recent discoveries have enhanced our understanding of the molecular pathogenesis of OCCCs, leading to new therapeutic opportunities. These include mutations in ARID1A, which provides a link to endometriosis, upreg ...[more]

PMID: 23558892

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Project description:BackgroundIt has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC).MethodsSeven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored.ResultsThe expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar results were observed in HGSC patients.ConclusionOvarian CCC showed a markedly different expression map of drug-based molecular biomarkers from HGSC, which suggested a new personalized target therapy in this rare subtype.

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New perspectives on molecular targeted therapy in ovarian clear cell carcinoma.

Publications

New perspectives on molecular targeted therapy in ovarian clear cell carcinoma.

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