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Olaparib response

MedGen UID:
830458
•Concept ID:
CN224080
•
Sign or Symptom
Synonym: Lynparza response
Drug:
Olaparib
MedGen UID:
412214
•Concept ID:
C2316164
•
Organic Chemical
A small molecule inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential chemosensitizing, radiosensitizing, and antineoplastic activities. Olaparib selectively binds to and inhibits PARP, inhibiting PARP-mediated repair of single strand DNA breaks; PARP inhibition may enhance the cytotoxicity of DNA-damaging agents and may reverse tumor cell chemoresistance and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins and can be activated by single-stranded DNA breaks. [from NCI]
Olaparib

Professional guidelines

PubMed

Consensus statements and treatment algorithm to guide clinicians in the selection of maintenance therapy for patients with newly diagnosed, advanced ovarian carcinoma: Results of a Delphi study.
Colombo N, Gadducci A, Landoni F, Lorusso D, Sabbatini R, Artioli G, Berardi R, Ceccherini R, Cecere SC, Cormio G, De Angelis C, Legge F, Lissoni A, Mammoliti S, Mangili G, Naglieri E, Petrella MC, Ricciardi GRR, Ronzino G, Salutari V, Sambataro D, Savarese A, Scandurra G, Tasca G, Tomao F, Valabrega G, Zavallone L, Pignata S
Gynecol Oncol 2023 Aug;175:182-189. Epub 2023 Jun 22 doi: 10.1016/j.ygyno.2023.05.065. PMID: 37355448
Management of patients with early-stage triple-negative breast cancer following pembrolizumab-based neoadjuvant therapy: What are the evidences?
Bonadio RC, Tarantino P, Testa L, Punie K, Pernas S, Barrios C, Curigliano G, Tolaney SM, Barroso-Sousa R
Cancer Treat Rev 2022 Nov;110:102459. Epub 2022 Aug 18 doi: 10.1016/j.ctrv.2022.102459. PMID: 35998514
PARP and PARG inhibitors in cancer treatment.
Slade D
Genes Dev 2020 Mar 1;34(5-6):360-394. Epub 2020 Feb 6 doi: 10.1101/gad.334516.119. PMID: 32029455Free PMC Article

Curated

DailyMed Drug Label, LYNPARZA- olaparib tablet, 2022

Recent clinical studies

Etiology

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC.
Sun C, Cao W, Qiu C, Li C, Dongol S, Zhang Z, Dong R, Song K, Yang X, Zhang Q, Kong B
J Hematol Oncol 2020 Jan 31;13(1):9. doi: 10.1186/s13045-020-0844-0. PMID: 32005272Free PMC Article
Augmentation of response to chemotherapy by microRNA-506 through regulation of RAD51 in serous ovarian cancers.
Liu G, Yang D, Rupaimoole R, Pecot CV, Sun Y, Mangala LS, Li X, Ji P, Cogdell D, Hu L, Wang Y, Rodriguez-Aguayo C, Lopez-Berestein G, Shmulevich I, De Cecco L, Chen K, Mezzanzanica D, Xue F, Sood AK, Zhang W
J Natl Cancer Inst 2015 Jul;107(7) Epub 2015 May 20 doi: 10.1093/jnci/djv108. PMID: 25995442Free PMC Article
Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval.
Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, De Greve J, Lubinski J, Shanley S, Messiou C, A'Hern R, Tutt A, Ashworth A, Stone J, Carmichael J, Schellens JH, de Bono JS, Kaye SB
J Clin Oncol 2010 May 20;28(15):2512-9. Epub 2010 Apr 20 doi: 10.1200/JCO.2009.26.9589. PMID: 20406929

Diagnosis

CDK inhibition results in pharmacologic BRCAness increasing sensitivity to olaparib in BRCA1-WT and olaparib resistant in Triple Negative Breast Cancer.
Orhan E, Velazquez C, Tabet I, Fenou L, Rodier G, Orsetti B, Jacot W, Sardet C, Theillet C
Cancer Lett 2024 May 1;589:216820. Epub 2024 Apr 3 doi: 10.1016/j.canlet.2024.216820. PMID: 38574883
Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma.
Xu Y, Spear S, Ma Y, Lorentzen MP, Gruet M, McKinney F, Xu Y, Wickremesinghe C, Shepherd MR, McNeish I, Keun HC, Nijhuis A
Cell Rep 2023 Oct 31;42(10):113307. Epub 2023 Oct 19 doi: 10.1016/j.celrep.2023.113307. PMID: 37858464
Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.
Coelho R, Tozzi A, Disler M, Lombardo F, Fedier A, López MN, Freuler F, Jacob F, Heinzelmann-Schwarz V
Cell Death Dis 2022 Oct 28;13(10):909. doi: 10.1038/s41419-022-05347-x. PMID: 36307400Free PMC Article
Basal expression of RAD51 foci predicts olaparib response in patient-derived ovarian cancer xenografts.
Guffanti F, Alvisi MF, Anastasia A, Ricci F, Chiappa M, Llop-Guevara A, Serra V, Fruscio R, Degasperi A, Nik-Zainal S, Bani MR, Lupia M, Giavazzi R, Rulli E, Damia G
Br J Cancer 2022 Jan;126(1):120-128. Epub 2021 Nov 3 doi: 10.1038/s41416-021-01609-1. PMID: 34732853Free PMC Article
MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC.
Sun C, Cao W, Qiu C, Li C, Dongol S, Zhang Z, Dong R, Song K, Yang X, Zhang Q, Kong B
J Hematol Oncol 2020 Jan 31;13(1):9. doi: 10.1186/s13045-020-0844-0. PMID: 32005272Free PMC Article

Therapy

CDK inhibition results in pharmacologic BRCAness increasing sensitivity to olaparib in BRCA1-WT and olaparib resistant in Triple Negative Breast Cancer.
Orhan E, Velazquez C, Tabet I, Fenou L, Rodier G, Orsetti B, Jacot W, Sardet C, Theillet C
Cancer Lett 2024 May 1;589:216820. Epub 2024 Apr 3 doi: 10.1016/j.canlet.2024.216820. PMID: 38574883
Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma.
Xu Y, Spear S, Ma Y, Lorentzen MP, Gruet M, McKinney F, Xu Y, Wickremesinghe C, Shepherd MR, McNeish I, Keun HC, Nijhuis A
Cell Rep 2023 Oct 31;42(10):113307. Epub 2023 Oct 19 doi: 10.1016/j.celrep.2023.113307. PMID: 37858464
Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.
Coelho R, Tozzi A, Disler M, Lombardo F, Fedier A, López MN, Freuler F, Jacob F, Heinzelmann-Schwarz V
Cell Death Dis 2022 Oct 28;13(10):909. doi: 10.1038/s41419-022-05347-x. PMID: 36307400Free PMC Article
Olaparib monotherapy as primary treatment in unselected triple negative breast cancer.
Eikesdal HP, Yndestad S, Elzawahry A, Llop-Guevara A, Gilje B, Blix ES, Espelid H, Lundgren S, Geisler J, Vagstad G, Venizelos A, Minsaas L, Leirvaag B, Gudlaugsson EG, Vintermyr OK, Aase HS, Aas T, Balmaña J, Serra V, Janssen EAM, Knappskog S, Lønning PE
Ann Oncol 2021 Feb;32(2):240-249. Epub 2020 Nov 24 doi: 10.1016/j.annonc.2020.11.009. PMID: 33242536
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE
J Clin Oncol 2020 Dec 20;38(36):4274-4282. Epub 2020 Oct 29 doi: 10.1200/JCO.20.02151. PMID: 33119476

Prognosis

Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma.
Xu Y, Spear S, Ma Y, Lorentzen MP, Gruet M, McKinney F, Xu Y, Wickremesinghe C, Shepherd MR, McNeish I, Keun HC, Nijhuis A
Cell Rep 2023 Oct 31;42(10):113307. Epub 2023 Oct 19 doi: 10.1016/j.celrep.2023.113307. PMID: 37858464
Normalized LST Is an Efficient Biomarker for Homologous Recombination Deficiency and Olaparib Response in Ovarian Carcinoma.
Christinat Y, Ho L, Clément S, Genestie C, Sehouli J, Cinieri S, Gonzalez Martin A, Denison U, Fujiwara K, Vergote I, Tognon G, Hietanen S, Ray-Coquard I, Pujade-Lauraine E, McKee TA
JCO Precis Oncol 2023 Jun;7:e2200555. doi: 10.1200/PO.22.00555. PMID: 37364234Free PMC Article
Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.
Coelho R, Tozzi A, Disler M, Lombardo F, Fedier A, López MN, Freuler F, Jacob F, Heinzelmann-Schwarz V
Cell Death Dis 2022 Oct 28;13(10):909. doi: 10.1038/s41419-022-05347-x. PMID: 36307400Free PMC Article
Basal expression of RAD51 foci predicts olaparib response in patient-derived ovarian cancer xenografts.
Guffanti F, Alvisi MF, Anastasia A, Ricci F, Chiappa M, Llop-Guevara A, Serra V, Fruscio R, Degasperi A, Nik-Zainal S, Bani MR, Lupia M, Giavazzi R, Rulli E, Damia G
Br J Cancer 2022 Jan;126(1):120-128. Epub 2021 Nov 3 doi: 10.1038/s41416-021-01609-1. PMID: 34732853Free PMC Article
Olaparib monotherapy as primary treatment in unselected triple negative breast cancer.
Eikesdal HP, Yndestad S, Elzawahry A, Llop-Guevara A, Gilje B, Blix ES, Espelid H, Lundgren S, Geisler J, Vagstad G, Venizelos A, Minsaas L, Leirvaag B, Gudlaugsson EG, Vintermyr OK, Aase HS, Aas T, Balmaña J, Serra V, Janssen EAM, Knappskog S, Lønning PE
Ann Oncol 2021 Feb;32(2):240-249. Epub 2020 Nov 24 doi: 10.1016/j.annonc.2020.11.009. PMID: 33242536

Clinical prediction guides

CDK inhibition results in pharmacologic BRCAness increasing sensitivity to olaparib in BRCA1-WT and olaparib resistant in Triple Negative Breast Cancer.
Orhan E, Velazquez C, Tabet I, Fenou L, Rodier G, Orsetti B, Jacot W, Sardet C, Theillet C
Cancer Lett 2024 May 1;589:216820. Epub 2024 Apr 3 doi: 10.1016/j.canlet.2024.216820. PMID: 38574883
Normalized LST Is an Efficient Biomarker for Homologous Recombination Deficiency and Olaparib Response in Ovarian Carcinoma.
Christinat Y, Ho L, Clément S, Genestie C, Sehouli J, Cinieri S, Gonzalez Martin A, Denison U, Fujiwara K, Vergote I, Tognon G, Hietanen S, Ray-Coquard I, Pujade-Lauraine E, McKee TA
JCO Precis Oncol 2023 Jun;7:e2200555. doi: 10.1200/PO.22.00555. PMID: 37364234Free PMC Article
Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.
Coelho R, Tozzi A, Disler M, Lombardo F, Fedier A, López MN, Freuler F, Jacob F, Heinzelmann-Schwarz V
Cell Death Dis 2022 Oct 28;13(10):909. doi: 10.1038/s41419-022-05347-x. PMID: 36307400Free PMC Article
Olaparib monotherapy as primary treatment in unselected triple negative breast cancer.
Eikesdal HP, Yndestad S, Elzawahry A, Llop-Guevara A, Gilje B, Blix ES, Espelid H, Lundgren S, Geisler J, Vagstad G, Venizelos A, Minsaas L, Leirvaag B, Gudlaugsson EG, Vintermyr OK, Aase HS, Aas T, Balmaña J, Serra V, Janssen EAM, Knappskog S, Lønning PE
Ann Oncol 2021 Feb;32(2):240-249. Epub 2020 Nov 24 doi: 10.1016/j.annonc.2020.11.009. PMID: 33242536
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE
J Clin Oncol 2020 Dec 20;38(36):4274-4282. Epub 2020 Oct 29 doi: 10.1200/JCO.20.02151. PMID: 33119476

Recent systematic reviews

Overlapping gene dependencies for PARP inhibitors and carboplatin response identified by functional CRISPR-Cas9 screening in ovarian cancer.
Coelho R, Tozzi A, Disler M, Lombardo F, Fedier A, López MN, Freuler F, Jacob F, Heinzelmann-Schwarz V
Cell Death Dis 2022 Oct 28;13(10):909. doi: 10.1038/s41419-022-05347-x. PMID: 36307400Free PMC Article

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