Note: The DNA damage response and cancer therapy

Note: The DNA damage response and cancer therapy_2012

Doi: 10.1038/nature10760

Future issues;

Pharmacological targeting 

• Biochemical and genetic interactions between the various DNA repair pws -- not clearly understood

• Having small potent inhibitors which specifically inhibits particular pw facilitating the interplay between DNA repair pws.

Cancer stem cells and tumor micro-environment

• Systemic knowledge in DNA damage and DDR in stem cells need to be explored

Genomic scar

• Cancer being classified according to their underlying pattern of pathogenic mutations

• Sequence scare -- reflects bot mutagens which tumor has been exposed to and repair processes that have to operated to mitigate their impact

• Example;

• HRD

• Microsatellite instability

• Mismatch repair is defective

• Matching molecular signatures of DNA mutation and repair -- require functional biomarkers -- which identify DDR defect and facilitate in the selection of therapy

• Example -- RAD51 foci formation

• Requiring genotoxic stress followed by a measurement of molecular response

• Challenges -- 

• Practical

• Logistical

• Tumor cells may not respond in the same way ex vivo as they do in vivo