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High-grade serous ovarian carcinoma, the “Achiles’ hill” for clinicians and molecular biologists: a molecular insight
High-grade serous ovarian carcinoma (HGSOC), the deadliest ovarian cancer, alone accounts for 90% of all its subtypes. Characterized by hallmark mutation of TP53, HGSOC show diverse molecular etiology. HGSOC can arise from both ovarian epithelium as well as the fimbrial epithelium of the fallopian t...
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Published in: | Molecular biology reports 2023-11, Vol.50 (11), p.9511-9519 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | High-grade serous ovarian carcinoma (HGSOC), the deadliest ovarian cancer, alone accounts for 90% of all its subtypes. Characterized by hallmark mutation of TP53, HGSOC show diverse molecular etiology. HGSOC can arise from both ovarian epithelium as well as the fimbrial epithelium of the fallopian tube. Ovulation induced reactive oxygen species, follicular fluid associated growth factor induced stemness, deregulation of hormone receptors like ER, FSHR, AR and hormones like FSH, LH, prolonged ovulation cycle, use of oral contraceptives are agonists of HGSOC while parity, breastfeeding provide protective effect from HGSOC development. Apart from a generic
TP53
mutation, mutation of
BRCA1/2
,
RAD51, BRIP1, PALB2, CHEK2, RAD50
etc., were reportedly associated with development of HGSOC. Epigenetic events like methylation of
RASSF1A
of RAS signaling pathway,
OR51L1, OR51I1, OR51F1
etc. has been reported in HGSOC. Micro-RNAs like miR-1290, miR 27-a-3p miR23a, miR205 were reportedly upregulated in HGSOC. Amongst its cognate subtypes viz. differentiated, immunoreactive, mesenchymal, and proliferative, mesenchymal, and proliferative show worst prognosis. A system biology approach showed five major altered pathways in HGSOC, namely, RB, PI3K/RAS, NOTCH, HRR and FOXM1 signaling. For chemonaive patients, drugs that helps in efflux of reduced glutathione or prevent the redox coupling of GSH-GSSG, like Cisplatin, could be considered as the best therapeutic choice for HGSOC. For patients with BRCA1/2 mutations, PARP inhibitors alone or with Bevacizumab can be effective. Immune checkpoint inhibitors could be effective against immunoreactive subtypes. Identification of genes deregulated in chemoresistance could provide better insights in dealing with the disease. |
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ISSN: | 0301-4851 1573-4978 |
DOI: | 10.1007/s11033-023-08760-3 |