Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models.

Compared with vehicle-treated animals (TAMs per μm 2 , 16.6±1.4 for SW-1990 and 82.8±4.6 for MIA PaCa-2), lurbinectedin treatment resulted in a highly significant reduction of TAMs in both SW-1990 (7.2±1.2, P =0.002) and MIA PaCa-2 (27.8±1.3, P =0.002) xenografts.

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Treatment with lurbinectedin or the lurbinectedin-gemcitabine combination of mice bearing MIA PaCa-2 tumors slightly reduced the Ki67 index as compared with vehicle-treated tumors, but these differences did not reach statistical significance ( Fig. 4 B, Fig. 5 D), suggesting that, in this cell line, the synergistic effect of the combination depends mainly on the induction of cell death and not on a proliferative blockage.

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