Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.

ABSTRACT: Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based

SUBMITTER: Basourakos SP 

PROVIDER: S-EPMC5471128 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature