Research Progress of M6A Methylation Modification in Immunotherapy of Colorectal Cancer.

Among the Poly(ADP-ribose) Polymerase (PARP) family in mammals, PARP1 is the first identified and well-studied member that plays a critical role in DNA damage repair and has been proven to be an effective target for cancer therapy. Here, we have reviewed not only the role of PARP1 in different DNA damage repair pathways, but also the working mech-anisms of several PARP inhibitors (PARPi), inhibiting Poly-ADP-ribosylation (PARylation) processing and PAR chains production to trap PARP1 on impaired DNA and inducing Tran-scription-replication Conflicts (TRCs) by inhibiting the PARP1 activity. This review has sys-tematically summarized the latest clinical application of six authorized PARPi, including olaparib, rucaparib, niraparib, talazoparib, fuzuloparib and pamiparib, in monotherapy and combination therapies with chemotherapy, radiotherapy, and immunotherapy, in different kinds of cancer. Furthermore, probable challenges in PARPi application and drug resistance mechanisms have also been discussed. Despite these challenges, further development of new PARP1 inhibitors appears promising as a valuable approach to cancer treatment.