RRD-251 enhances the effects of gemcitabine to inhibit tumor growth. A, B, While gemcitabine-resistant variant L3.6plGemRes continue to grow in the presence of gemcitabine, growth was significantly inhibited in the RRD-251 group and abrogated with combination therapy (*p<0.01). In L3.6pl cells, gemcitabine resulted in regression of disease, RRD-251 stabilized growth, and combination therapy almost completely abolished tumor growth (*p<0.01). C, D, Tumors in vivo (L3.6pl, left flank and L3.6plGemRes, right flank) and ex vivo {L3.6pl, a) and L3.6plGemRes, b)} demonstrating the differences in tumor size of the L3.6plGemRes {right flank, b)}in the presence of gemcitabine and also the significant inhibitory effect of RRD-251 alone and in combination with gemcitabine on both tumors regardless of gemcitabine sensitivity.