Specific targeting of the KRAS mutational landscape in myeloma as a tool to unveil the elicited antitumor activity.

ABSTRACT: Alterations in KRAS have been identified as the most recurring somatic variants in the multiple myeloma (MM) mutational landscape. Combining DNA and RNA sequencing, we studied 756 patients and observed KRAS as the most frequently mutated gene in patients at diagnosis; in addition, we demonstrated the persistence or de novo occurrence of the KRAS aberration at disease relapse. Small-molecule inhibitors targeting KRAS have been developed; however, they are selective for tumors carrying the KRASG12C mutation. 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 used AZD4785, a potent and selective antisense oligonucleotide that selectively targets and downregulates all KRAS isoforms, as a too

SUBMITTER: Sacco A 

PROVIDER: S-EPMC9710471 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature