Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review)

Abstract

With the development of precision medicine, targeted therapy has attracted extensive attention. Poly(ADP‑ribose) polymerase inhibitors (PARPi) are critical clinical drugs designed to induce cell death and are major antitumor targeted agents. However, preclinical and clinical data have revealed the limitations of PARPi monotherapy. Therefore, their combination with other targeted drugs has become a research hotspot in tumor treatment. Recent studies have demonstrated the critical role of small molecular inhibitors in multiple haematological cancers and solid tumors via cellular signalling modulation, exhibiting potential as a combined pharmacotherapy. In the present review, studies focused on small molecular inhibitors targeting the homologous recombination pathway were summarized and clinical trials evaluating the safety and efficacy of combined treatment were discussed.

Keywords: DNA damage response; PARP inhibitors; clinical trials; combination therapy; small molecular inhibitors.

Figure 1

Small molecular inhibitors in DNA damage and DNA damage repair. Potential mechanisms of PARP inhibitor plus small molecular inhibitors combination treatment. PARP, poly(ADP ribose) polymerase; NHEJ, non-homologous end-joining; HRR, homologous recombination repair; ATM, ataxia telangiectasia-mutated gene; IGFBP-3-NONO/SFPQ, insulin-like growth factor binding protein-3-NONO/SFPQ; BRCA, breast cancer associated gene; RRM2, ribonucleotide reductase regulatory subunit M2; Chk-1, checkpoint kinase 1.