Combined PARP and Immune Checkpoint Inhibition in Ovarian Cancer

Elizabeth K Lee; Panagiotis A Konstantinopoulos

doi:10.1016/j.trecan.2019.06.004

Combined PARP and Immune Checkpoint Inhibition in Ovarian Cancer

Trends Cancer. 2019 Sep;5(9):524-528. doi: 10.1016/j.trecan.2019.06.004. Epub 2019 Jul 15.

Authors

Elizabeth K Lee¹, Panagiotis A Konstantinopoulos²

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Division of Gynecologic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].

PMID: 31474356
DOI: 10.1016/j.trecan.2019.06.004

Abstract

Recent studies have demonstrated that, besides direct cytotoxic effects, poly(ADP ribose) polymerase (PARP) inhibitors (PARPis) exhibit antitumor immunity that occurs in a stimulator of interferon genes (STING)-dependent manner and is augmented by immune checkpoint blockade (CPB). In ovarian cancer, combined PARP and immune checkpoint inhibition has yielded encouraging preliminary results in two early-phase clinical trials and is currently being evaluated in both first-line and recurrent settings.

Keywords: PARP inhibitor; PD-1 inhibitor; STING pathway; checkpoint blockade; immunotherapy; ovarian cancer.

Publication types

Review

MeSH terms

Antineoplastic Agents, Immunological / pharmacology*
Antineoplastic Agents, Immunological / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
B7-H1 Antigen / antagonists & inhibitors
B7-H1 Antigen / immunology
Clinical Trials as Topic
Drug Synergism
Female
Humans
Membrane Proteins / immunology
Membrane Proteins / metabolism
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / immunology
Ovarian Neoplasms / pathology
Poly (ADP-Ribose) Polymerase-1 / antagonists & inhibitors
Poly (ADP-Ribose) Polymerase-1 / metabolism
Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / immunology
Signal Transduction / drug effects
Signal Transduction / immunology
Treatment Outcome

Substances

Antineoplastic Agents, Immunological
B7-H1 Antigen
CD274 protein, human
Membrane Proteins
PDCD1 protein, human
Poly(ADP-ribose) Polymerase Inhibitors
Programmed Cell Death 1 Receptor
STING1 protein, human
PARP1 protein, human
Poly (ADP-Ribose) Polymerase-1