78 / 116
The paradox index (PI) is defined as the ratio between, BRAFi capacity to inhibit the
activated product of the MAPK pathway (= phospho-ERK) in tumor cells and their ability
to induce ERK activation in healthy cells.
Paradox index definition
The larger is the PI, the less the treatment induces cutaneous adverse events for
therapeutic concentrations
Paradox Index= EC80 / IC80
Definitions:
•
EC80:
Concentration which induces 80% of ERK phosphorylation in healthy cells
•
IC80:
Concentration which reduces by 80% cell proliferation in tumor cells
Adelmann et al., 2016, Oncotarget
Figure 1: Compound with a small paradox index (restricted PI)
IC80
EC80
IC80
EC80
Melanoma cells
proliferation
Melanoma cells
proliferation
ERK phosphorilation
in healthy cells
ERK phosphorilation
in healthy cells
Concentration
Concentration
Figure 2: Compound with a large paradox index (favourable PI)