Oncogenic mutation of RAS occurs in 20-25% of all malignancies. Our research group have examined inhibition of RAS prenylation on RAS wild type and RAS mutated melanoma, colorectal cancer and lung adenocarcinoma cell lines. Effects of clinically approved bisphosphonate (zoledronic acid) and its lipophilic derivate (BPH1222) on cell viability and cell signaling were determined. In models of melanoma and colorectal cancer we found no relevant difference in sensitivity to the drugs in light of RAS mutation presence. In case of lung adenocarcinoma bisphosphonate treatment inhibited both wild-type and mutated K-RAS, although tumor cells carrying mutated K-RAS seemed to be more sensitive to the bisphosphonate treatment. In summary, further investigations are warranted to identify tumor subgroups where bisphosphonates could have an effective therapeutic potential.
|Translated title of the contribution||Impact of prenylation inhibition on ras mutant tumors in preclinical studies|
|Number of pages||10|
|Publication status||Published - Jan 1 2019|
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