RESUMO
Fanconi anemia (FA) is an inheritable disorder that presents with bone marrow failure, developmental anomalies, and an increased susceptibility to cancer. The etiology of this condition stems from a genetic mutation that disrupts the proper repair of interstrand DNA cross-links (ICLs). The resultant dysregulation of the DNA damage response mechanism can induce genomic instability, thereby elevating the mutation rates and the likelihood of developing cancer. The FA pathway assumes a pivotal role in safeguarding genome stability through its involvement in the repair of DNA cross-links and the maintenance of overall genomic integrity. A mutation in the germ line of any of the genes responsible for encoding the FA protein results in the development of FA. The prevalence of aberrant FA gene expression in somatic cancer, coupled with the identification of a connection between FA pathway activation and resistance to chemotherapy, has solidified the correlation between the FA pathway and cancer. Consequently, targeted therapies that exploit FA pathway gene abnormalities are being progressively developed and implemented. This review critically examines the involvement of the FA protein in the repair of ICLs, the regulation of the FA signaling network, and its implications in cancer pathogenesis and prognosis. Additionally, it explores the potential utility of small-molecule inhibitors that target the FA pathway.
RESUMO
@#Poly(ADP-ribose)polymerase-1(PARP-1)plays a vital role in the regulation of DNA repair and apoptosis. Breakthrough has been made in the treatment of cancer with PARP-1 inhibitors, but the emergence of drug resistance has limited its further application in clinic. This paper reviews advances in the research on PARP-1 inhibitors combined with other drugs to overcome drug resistance, highlights and evaluates the existing drug combination strategies and their therapeutic effects in clinical practice. It is proposed that the development of dual-target or multi-target drugs will become a promising approach to overcome the resistance of PARP-1 inhibitors and broaden their indications.