Dual Actions of Ketorolac in Metastatic Ovarian Cancer.
Cdc42
Rac1
ketorolac
metastasis
non-steroidal anti-inflammatory drug (NSAID)
ovarian cancer
peri-operative period
therapeutic targets
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
24 Jul 2019
24 Jul 2019
Historique:
received:
24
06
2019
revised:
11
07
2019
accepted:
17
07
2019
entrez:
27
7
2019
pubmed:
28
7
2019
medline:
28
7
2019
Statut:
epublish
Résumé
Cytoreductive surgery and chemotherapy are cornerstones of ovarian cancer treatment, yet disease recurrence remains a significant clinical issue. Surgery can release cancer cells into the circulation, suppress anti-tumor immunity, and induce inflammatory responses that support the growth of residual disease. Intervention within the peri-operative window is an under-explored opportunity to mitigate these consequences of surgery and influence the course of metastatic disease to improve patient outcomes. One drug associated with improved survival in cancer patients is ketorolac. Ketorolac is a chiral molecule administered as a 1:1 racemic mixture of the S- and R-enantiomers. The S-enantiomer is considered the active component for its FDA indication in pain management with selective activity against cyclooxygenase (COX) enzymes. The R-enantiomer has a previously unrecognized activity as an inhibitor of Rac1 (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42) GTPases. Therefore, ketorolac differs from other non-steroidal anti-inflammatory drugs (NSAIDs) by functioning as two distinct pharmacologic entities due to the independent actions of each enantiomer. In this review, we summarize evidence supporting the benefits of ketorolac administration for ovarian cancer patients. We also discuss how simultaneous inhibition of these two distinct classes of targets, COX enzymes and Rac1/Cdc42, by S-ketorolac and R-ketorolac respectively, could each contribute to anti-cancer activity.
Identifiants
pubmed: 31344967
pii: cancers11081049
doi: 10.3390/cancers11081049
pmc: PMC6721416
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : P30 CA118100
Pays : United States
Organisme : NIH HHS
ID : NCATS R21TR001731
Pays : United States
Organisme : NIH HHS
ID : P50 GM085273
Pays : United States
Organisme : NIH HHS
ID : P30 CA118100
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM085273
Pays : United States
Organisme : NCATS NIH HHS
ID : R21 TR001731
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.
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