Eliminating hypoxic tumor cells improves response to PARP inhibitors in homologous recombination-deficient cancer models

Hypoxia, a hallmark feature of the tumor microenvironment, causes resistance to conventional chemotherapy, but was recently reported to synergize with poly(ADP-ribose) polymerase inhibitors (PARPis) in homologous recombination-proficient (HR-proficient) cells through suppression of HR. While this sy...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	The Journal of clinical investigation 2021-06, Vol.131 (11), p.1-17
Hauptverfasser:	Mehibel, Manal, Xu, Yu, Li, Caiyun G, Moon, Eui Jung, Thakkar, Kaushik N, Diep, Anh N, Kim, Ryan K, Bloomstein, Joshua D, Xiao, Yiren, Bacal, Julien, Saldivar, Joshua C, Le, Quynh-Thu, Cimprich, Karlene A, Rankin, Erinn B, Giaccia, Amato J
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antitumor activity Biomedical research Breast cancer Cancer Cancer cells Cancer therapies Care and treatment Cell Hypoxia - drug effects Cell Hypoxia - genetics Cell Line, Tumor Chemotherapy Cytotoxicity DNA Damage DNA repair Drug dosages Drug resistance Drug therapy Enzymes Female Gene expression Homologous Recombination Humans Hypoxia Mice Mice, Nude Mutation Neoplasms, Experimental - drug therapy Neoplasms, Experimental - genetics Neoplasms, Experimental - metabolism Oxygen Physiological aspects Poly(ADP-ribose) Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Proteins Reactive Oxygen Species - metabolism Response rates Ribose Synergism Targeted cancer therapy Tirapazamine Toxicity Tumor cells Tumor microenvironment Tumors Xenograft Model Antitumor Assays
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Hypoxia, a hallmark feature of the tumor microenvironment, causes resistance to conventional chemotherapy, but was recently reported to synergize with poly(ADP-ribose) polymerase inhibitors (PARPis) in homologous recombination-proficient (HR-proficient) cells through suppression of HR. While this synergistic killing occurs under severe hypoxia (
ISSN:	1558-8238 0021-9738 1558-8238
DOI:	10.1172/JCI146256