PARPi + Antiangiogenic Therapy
•
Concept: “BRCA-like” behavior
- Contextual Synthetic lethality
•
Hypoxia: reduction of key HRR proteins
(RAD51, BRCA, MSH) and increased
circulating endothelial cells
•
VEGFR3 inhibition
- downregulates
RAD51
,
BRCA
expression
- restores chemosensitivity in resistant
BRCA2
cell lines
- Preclinical data: synergy Olaparib-
Cediranib on cell invasion/cell tube
organization
Hegan et al.,
PNAS
2010; Lim J, et al Neoplasia 2014
