Optimizing poly (ADP-ribose) polymerase inhibition through combined epigenetic and immunotherapy

Cancer Science
Thiru PrasannaSudha Rao

Abstract

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor survival outcomes. Currently, there are no targeted therapies available for TNBCs despite remarkable progress in targeted and immune-directed therapies for other solid organ malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective anticancer drugs that produce good initial clinical responses, especially in homologous recombination DNA repair-deficient cancers. However, resistance is the rule rather than the exception, and recurrent tumors tend to have an aggressive phenotype associated with poor survival. Many efforts have been made to overcome PARPi resistance, mostly by targeting genes and effector proteins participating in homologous recombination that are overexpressed during PARPi therapy. Due to many known and unknown compensatory pathways, genes, and effector proteins, overlap and shared resistance are common. Overexpression of programmed cell death-ligand 1 (PD-L1) and cancer stem cell (CSC) sparing are novel PARPi resistance hypotheses. Although adding programmed cell death-1 (PD-1)/PD-L1 inhibitors to PARPi might improve immunogenic cell death and be crucial for durable responses, they are less likely to target the...Continue Reading

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Citations

Feb 23, 2019·Journal of Experimental & Clinical Cancer Research : CR·Daniela CriscuoloAngela Celetti
Jun 12, 2019·Biochemical Pharmacology·Alice RaineriMarta Menegazzi
May 1, 2021·Journal of Personalized Medicine·Florian G KleinRoman Nawroth
Aug 8, 2021·International Journal of Molecular Sciences·Hsing-Ju Wu, Pei-Yi Chu
Aug 10, 2021·Environmental Science and Pollution Research International·Lina ZhouYinyan He
Sep 29, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·E Gabriela ChioreanHoward S Hochster

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Methods Mentioned

BETA
acetylation

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