[en] KRAS is a frequently mutated oncogene in lung cancer and among the most refractory to EGFR targeted therapy. Recently, preclinical evidence in pancreatic cancer has demonstrated that mutant KRAS can be regulated by EGFR. However, the distinct correlation between the EGFR/HER family members and mutant KRAS has not been investigated. Here, we show that non-small cell lung cancer cell lines harboring differing isoforms of mutant KRAS, can be broadly divided into EGFR/HER dependent and EGFR/HER independent groups. Combined therapeutic targeting of EGFR, HER2 and HER3 in isoforms regulated by extracellular growth signals promotes in vitro and in vivo efficacy. We also provide evidence that depletion of EGFR via RNA interference specifically abolishes the EGFR/KRAS interaction in the dependent subset. Taken together, these findings suggest that upstream inhibition of the EGFR/HER receptors may be effective in treating a subset of KRAS mutant lung cancers.
Disciplines :
Oncology
Author, co-author :
Umelo, Ijeoma ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
De Wever, Olivier
Kronenberger, Peter
Van Deun, Jan
Noor, Alfiah
Singh, Kshitiz
Teugels, Erik
Chen, Gang
Bracke, Marc
De Greve, Jacques
Language :
English
Title :
Combined targeting of EGFR/HER promotes anti-tumor efficacy in subsets of KRAS mutant lung cancer resistant to single EGFR blockade.
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