Immunomodulatory roles of PARP-1 and PARP-2: impact on PARP-centered cancer therapies
| Autor: | José Yélamos, Syed O. Ali, Jaime Jimeno, Lucia Moreno-Lama |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research DNA damage DNA repair Review Biology medicine.disease_cause lcsh:RC254-282 PARP Immunomodulation 03 medical and health sciences 0302 clinical medicine Immune system medicine Tumor microenvironment Cancer lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Acquired immune system medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Carcinogenesis |
| Zdroj: | Cancers Cancers, Vol 12, Iss 2, p 392 (2020) |
| Popis: | Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 are enzymes which post-translationally modify proteins through poly(ADP-ribosyl)ation (PARylation)-the transfer of ADP-ribose chains onto amino acid residues-with a resultant modulation of protein function. Many targets of PARP-1/2-dependent PARylation are involved in the DNA damage response and hence, the loss of these proteins disrupts a wide range of biological processes, from DNA repair and epigenetics to telomere and centromere regulation. The central role of these PARPs in DNA metabolism in cancer cells has led to the development of PARP inhibitors as new cancer therapeutics, both as adjuvant treatment potentiating chemo-, radio-, and immuno-therapies and as monotherapy exploiting cancer-specific defects in DNA repair. However, a cancer is not just made up of cancer cells and the tumor microenvironment also includes multiple other cell types, particularly stromal and immune cells. Interactions between these cells-cancerous and non-cancerous-are known to either favor or limit tumorigenesis. In recent years, an important role of PARP-1 and PARP-2 has been demonstrated in different aspects of the immune response, modulating both the innate and adaptive immune system. It is now emerging that PARP-1 and PARP-2 may not only impact cancer cell biology, but also modulate the anti-tumor immune response. Understanding the immunomodulatory roles of PARP-1 and PARP-2 may provide invaluable clues to the rational development of more selective PARP-centered therapies which target both the cancer and its microenvironment. This research was funded by The Fundación Científica de la Asociación Española Contra el Cáncer (AECC), grant number PROYEI6018YÉLA, and the Spanish Ministerio de Economía, Industria y Competitividad, grant number SAF2017-83565-R. |
| Databáze: | OpenAIRE |
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