A research from C Denoyelle and B Lambert reports that EGFR inhibitor and the BH3-mimetic molecule ABT-737 synergize in the killing of ovarian cancer cell lines.

They wondered whether the association of an anti-EGFR monoclonal antibody (cetuximab) or EGFR TKIs (erlotinib and gefitinib) with a BH3-mimetic molecule (ABT-737), which binds and neutralizes BCL-X_L, could have the same effect as miR-491-5p. Indeed, the combination of these different EGFR inhibitors with ABT-737 (or siRNA-BCL-X_L) induced apoptosis in IGROV1-R10 cells, whereas each drug alone had no obvious effect.

Moreover, they observed that this combination could be also effective in the ovarian cancer cell line OVCAR-3. Indeed, whereas ABT-737 induced a mild apoptosis, the combination of EGFR TKI (erlotinib or gefitinib) with a BH3-mimetic molecule led to a massive apoptosis in OVCAR-3 cells .

Altogether, these observations highlight the interest in pursuing a combination therapy of an EGFR inhibitor with a BH3-mimetic molecule in ovarian cancer. Finally, as expected with our previous results obtained with miR-491-5p, the combination of cetuximab (or erlotinib or gefitinib) and ABT-737 (or siRNA-BCL-X_L) did not induce cell death in SKOV3 cells.