Multiomics analysis of serial PARP inhibitor treated metastatic TNBC inform on rational combination therapies.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
19 Oct 2021
19 Oct 2021
Historique:
received:
08
10
2020
accepted:
22
09
2021
entrez:
20
10
2021
pubmed:
21
10
2021
medline:
21
10
2021
Statut:
epublish
Résumé
In a pilot study, we evaluated the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities as they emerge under therapeutic stress engendered by poly-ADP-ribose polymerase (PARP) inhibitors (PARPi). In a BRCA-mutant basal breast cancer exceptional long-term survivor, a striking tumor destruction was accompanied by a marked infiltration of immune cells containing CD8 effector cells, consistent with pre-clinical evidence for association between STING mediated immune activation and benefit from PARPi and immunotherapy. Tumor cells in the exceptional responder underwent extensive protein network rewiring in response to PARP inhibition. In contrast, there were minimal changes in the ecosystem of a luminal androgen receptor rapid progressor, likely due to indifference to the effects of PARP inhibition. Together, identification of PARPi-induced emergent changes could be used to select patient specific combination therapies, based on tumor and immune state changes.
Identifiants
pubmed: 34667258
doi: 10.1038/s41698-021-00232-w
pii: 10.1038/s41698-021-00232-w
pmc: PMC8526613
doi:
Types de publication
Journal Article
Langues
eng
Pagination
92Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK117459
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA232819
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA231877
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG008100
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217842
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199315
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA195469
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209988
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA069533
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233280
Pays : United States
Organisme : BLRD VA
ID : I01 BX002842
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210957
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM086688
Pays : United States
Informations de copyright
© 2021. The Author(s).
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