The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer
Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20-30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
|---|---|
| Enthalten in: |
Journal of clinical medicine - 9(2020), 7 vom: 15. Juli |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dion, Ludivine [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
BRCA |
|---|
| Anmerkungen: |
Date Revised 28.09.2020 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/jcm9072239 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM312560044 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM312560044 | ||
| 003 | DE-627 | ||
| 005 | 20231225144655.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/jcm9072239 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1041.xml |
| 035 | |a (DE-627)NLM312560044 | ||
| 035 | |a (NLM)32679669 | ||
| 035 | |a (PII)E2239 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dion, Ludivine |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 28.09.2020 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Epithelial ovarian cancer (EOC) affects 43,000 women worldwide every year and has a five-year survival rate of 30%. Mainstay treatment is extensive surgery and chemotherapy. Outcomes could be improved by molecular profiling. We conducted a review of the literature to identify relevant publications on molecular and genetic alterations in EOC. Approximately 15% of all EOCs are due to BRCA1 or BRCA2 mutations. Four histologic subtypes characterized by different mutations have been described: serous, endometrioid, mucinous, and clear-cell. Between 20-30% of high-grade serous EOCs have a BRCA mutation. Tumors with BRCA mutations are unable to repair double-strand DNA breaks, making them more sensitive to platinum-based chemotherapy and to PolyAdenosine Diphosphate-Ribose Polymerase (PARP) inhibitors. Olaparib is a PARP inhibitor with proven efficacy in BRCA-mutated ovarian cancer, but its effectiveness remains to be demonstrated in tumors with a BRCAness (breast cancer) profile (i.e., also including sporadic tumors in patients with deficient DNA repair genes). A universally accepted molecular definition of BRCAness is required to identify optimal theranostic strategies involving PARP inhibitors. Gene expression analyses have led to the identification of four subgroups of high-grade serous EOC: mesenchymal, proliferative, differentiated, and immunoreactive. These subtypes are not mutually exclusive but are correlated with prognosis. They are not yet used in routine clinical practice. A greater understanding of EOC subtypes could improve patient management | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a BRCA | |
| 650 | 4 | |a BRCAness profile | |
| 650 | 4 | |a molecular subtypes | |
| 650 | 4 | |a ovarian cancer | |
| 650 | 4 | |a therapeutic approach | |
| 700 | 1 | |a Carton, Isis |e verfasserin |4 aut | |
| 700 | 1 | |a Jaillard, Sylvie |e verfasserin |4 aut | |
| 700 | 1 | |a Nyangoh Timoh, Krystel |e verfasserin |4 aut | |
| 700 | 1 | |a Henno, Sébastien |e verfasserin |4 aut | |
| 700 | 1 | |a Sardain, Hugo |e verfasserin |4 aut | |
| 700 | 1 | |a Foucher, Fabrice |e verfasserin |4 aut | |
| 700 | 1 | |a Levêque, Jean |e verfasserin |4 aut | |
| 700 | 1 | |a de la Motte Rouge, Thibault |e verfasserin |4 aut | |
| 700 | 1 | |a Brousse, Susie |e verfasserin |4 aut | |
| 700 | 1 | |a Lavoué, Vincent |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of clinical medicine |d 2012 |g 9(2020), 7 vom: 15. Juli |w (DE-627)NLM230666310 |x 2077-0383 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2020 |g number:7 |g day:15 |g month:07 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/jcm9072239 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2020 |e 7 |b 15 |c 07 | ||