Repressing DNA Repair to Enhance Chemotherapy: Targeting MyD88 in Colon Cancer
Menée in vitro et à l'aide de xénogreffes, cette étude met en évidence le rôlé joué par la protéine MyD88 dans des mécanismes liés à l'inflammation, la réparation de l'ADN et la résistance de cellules cancéreuses à un agent génotoxique
The more a cell divides, the more unstable its DNA is and the more DNA damage it sustains during replication. Thus, cells often require DNA repair to simply progress through a DNA replication cycle. Cancer cells are especially sensitive to this requirement for DNA repair because they replicate their DNA without most of the controls normal cells have. Thus, cancer cells subvert DNA repair pathways to maintain replication, and prevent apoptosis from mitotic catastrophe [reviewed in (1)]. This enhancement of DNA repair is further selected for by cancer therapy and commonly leads to resistance. The paradox of this is that many cancers have defects in DNA repair that lead to their original genomic instability and transformation to malignancy in the first place.
Cancer cells resolve this paradox by becoming increasingly reliant on, indeed addicted to, alternative DNA repair pathways for replication (1). Targeting these alternative DNA repair pathways can lead to not only decreases in proliferation but also increases in de novo DNA lesions during replication and ultimately apoptosis. Such targeting of DNA repair is one form of synthetic lethality, which is one of the most promising drug development concepts in the last decade (1). Synthetic lethality is especially intriguing in malignancies that are less responsive to classic cytotoxic chemotherapy, such …
Journal of the National Cancer Institute , éditorial, 2013