Inhibition of a pancreatic cancer model by cooperative pairs of clinically approved and experimental antibodies

Ruth Maron, Bilha Schechter, Nishanth Belugali Nataraj, Soma Ghosh, Donatella Romaniello, Ilaria Marrocco, Ashish Noronha, Silvia Carvalho, Yosef Yarden, Michael Sela

Risultato della ricerca: Contributo in rivistaArticolo in rivista


By year 2025 pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer related death. However, other than improved chemotherapy and a small molecule inhibitor of the epidermal growth factor receptor (EGFR), no targeted drugs are currently available. Repurposing of approved drugs might offer a rapid solution. We employed an animal PDAC model, expressing a mutant and a wild type form of p53 and KRAS, respectively. Cetuximab, a clinically approved anti-EGFR monoclonal antibody (mAb) weakly inhibited PDAC xenografts, similar to trastuzumab, a mAb against HER2, a co-receptor of EGFR. Because the combination of cetuximab and trastuzumab only moderately enhanced the anti-tumor effects, we combined each with a home-made mAb to the same receptor and identified two cooperative pairs. The pair of trastuzumab and a murine anti-HER2 mAb better than the anti-EGFR pair inhibited PDAC xenografts, although HER2's abundance in our model is 15-fold lower than the level of EGFR. In vitro studies attribute cooperation to forced receptor endocytosis/degradation and inhibition of both DNA synthesis and cell migration. Taken together, our results identify cooperative pairs of anti-PDAC antibodies and highlight potential mechanisms of anti-tumor effects.
Lingua originaleEnglish
pagine (da-a)219-225
Numero di pagine7
RivistaBiochemical and Biophysical Research Communications
Stato di pubblicazionePubblicato - 2019


  • HER2/ERBB2
  • Homo-combination
  • Monoclonal antibody
  • Pancreatic cancer


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