Table 1.

Summary of AZD6738 sensitivity and synergy with gemcitabine across the panel of PDAC cell lines

AZD6738 GR50SUM_SYN_ANTSUM_SYN_ANT_WEIGHTEDSYN_MAXSYN_SPREAD
Without gemWith gemLOEWEBLISSAVGLOEWEBLISSAVGLOEWEBLISSAVGLOEWEBLISSAVG
MOUSE LINESK8484536158Gem 5 nmol/L51184861132210.800.620.71
TB32048710355112217915122337300.800.790.79
DT80827633950840532323230.520.660.59
TB31456771359133122919142966470.690.700.69
KPCFT7965326091346Gem 10 nmol/L15292261393655450.680.730.71
HUMAN LINESSW199093514561335232132324241.611.271.44
Capan-11572216531483616263535351.521.281.40
ASPC119836915131412413182926271.431.321.38
HPAFII32394279039643912253821291.621.571.60
Capan-2477522086257601210113333331.521.481.50
MiaPaCa-298448549185885749535260561.371.231.30
Panc-1>3000034961661351519674856157591.761.651.71
  • NOTE: GR50 for all cell lines was obtained using the GR metrics R package (developed by Clarke and colleagues, 2017). Mouse and human lines are ranked by increasing GR50 for AZD6738. Summing of synergy and antagonism was used to compare combinations using Metrics obtained from Combenefit. Both Bliss, Loewe models, and the average (AVG) are shown. SUM_SYN_ANT is the sum of synergy and antagonism observed in concentration logarithmic space. For instance, an integrated synergy of 50 is equivalent to an extrasynergistic effect of 50%, which is spread over a square of 1 log x 1 log in the 2-d log-concentration space. Both antagonistic and synergistic effects are considered in this metric. The integrated weighted synergy SUM_SYN_ANT_WEIGHTED incorporates a weight based on the dose response, which biases the total score toward synergy achieving highest effect. Hence, a synergy of 50% leading to a combined full effect (100%) will have more weight than if the corresponding effect was only 20% or 30%. Both antagonistic and synergistic effects are considered in this metric. SYN_MAX is the maximum level of synergy observed. SYN_SPREAD is a measure of synergy spread in the logarithmic concentration space.