AZD4785

Therefore, there is still a need to develop novel therapeutic approaches to target the KRAS mutational events found in other tumor types, including MM. We have used AZD4785, a potent and selective antisense oligonucleotide (ASO) which selectively targets and down-regulates all KRAS isoforms, as a tool to dissect the functional sequelae secondary to KRAS silencing in MM within the context of the bone marrow niche; and demonstrated its ability to significantly silence KRAS, leading to inhibition of MM tumor growth, both in vitro and in vivo, confirming KRAS as a driver and a therapeutic target in MM.

Synergism between AZD4785 and bortezomib, in modulating MM growth was tested. CONCLUSION. Taken together, these data suggest that AZD4785 may represent a novel therapeutic approach for targeting mutant KRAS in MM, either alone or in combination with proteasome inhibitors; and warrant further development.