Cancers, Vol. 13, Pages 1392: Alternative Non-Homologous End-Joining: Error-Prone DNA Repair as Cancer ’s Achilles’ Heel

Cancers, Vol. 13, Pages 1392: Alternative Non-Homologous End-Joining: Error-Prone DNA Repair as Cancer’s Achilles’ Heel Cancers doi: 10.3390/cancers13061392 Authors: Daniele Caracciolo Caterina Riillo Maria Teresa Di Martino Pierosandro Tagliaferri Pierfrancesco Tassone Error-prone DNA repair pathways promote genomic instability which leads to the onset of cancer hallmarks by progressive genetic aberrations in tumor cells. The molecular mechanisms which foster this process remain mostly undefined, and breakthrough advancements are eagerly awaited. In this context, the alternative non-homologous end joining (Alt-NHEJ) pathway is considered a leading actor. Indeed, there is experimental evidence that up-regulation of major Alt-NHEJ components, such as LIG3, PolQ, and PARP1, occurs in different tumors, where they are often associated with disease progression and drug resistance. Moreover, the Alt-NHEJ addiction of cancer cells provides a promising target to be exploited by synthetic lethality approaches for the use of DNA damage response (DDR) inhibitors and even as a sensitizer to checkpoint-inhibitors immunotherapy by increasing the mutational load. In this review, we discuss recent findings highlighting the role of Alt-NHEJ as a promoter of genomic instability and, therefore, as new cancer’s Achilles’ heel to be therapeutically exploited in precision oncology.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research