Enhancing the anti-tumor response by combining DNA damage repair inhibitors in the treatment of solid tumors

• Published in: Biochimica et biophysica acta. Reviews on cancer Vol. 1878; no. 4; p. 188910
• Main Authors: Yu, Xianzhe, Zhu, Lingling, Wang, Ting, Li, Lu, Liu, Jiewei, Che, Guowei, Zhou, Qinghua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2023
• Subjects: DNA Damage; DNA damage repair inhibitor; DNA Repair; Humans; Immune checkpoint blockade; Immunotherapy; Neoplasms - drug therapy; Neoplasms - genetics; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; polyadenosine diphosphate ribose polymerase inhibitors; Solid cancer; PAR; BC; HR; POLθ; IFN; mCRPC; TNBC; DSBs; DNA damage repair inhibitor; ORRs; DDRis; DNA-PK; PARPis; VBR; TMB; polyadenosine diphosphate ribose polymerase inhibitors; ICB; IR; TME; Solid cancer; Immune checkpoint blockade; SSBs; ATM; HRD; NHEJ; HER2; CRPC; ATR
• ISSN: 0304-419X; 1879-2561
• DOI: 10.1016/j.bbcan.2023.188910

The anti-cancer efficacy of anti-malignancy therapies is related to DNA damage. However, DNA damage-response mechanisms can repair DNA damage, failing anti-tumor therapy. The resistance to chemotherapy, radiotherapy, and immunotherapy remains a clinical challenge. Thus, new strategies to overcome these therapeutic resistance mechanisms are needed. DNA damage repair inhibitors (DDRis) continue to be investigated, with polyadenosine diphosphate ribose polymerase inhibitors being the most studied inhibitors. Evidence of their clinical benefits and therapeutic potential in preclinical studies is growing. In addition to their potential as a monotherapy, DDRis may play an important synergistic role with other anti-cancer therapies or in reversing acquired treatment resistance. Here we review the impact of DDRis on solid tumors and the potential value of combinations of different treatment modalities with DDRis for solid tumors.