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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 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, and confirming KRAS as a driver and therapeutic target in MM.<\/jats:p>","DOI":"10.1182\/blood.2020010572","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T06:35:02Z","timestamp":1622702102000},"page":"1705-1720","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":22,"title":["Specific targeting of the KRAS mutational landscape in myeloma as a tool to unveil the elicited antitumor activity"],"prefix":"10.1182","volume":"138","author":[{"given":"Antonio","family":"Sacco","sequence":"first","affiliation":[{"name":"Clinical Research Development and Phase I Unit, CREA Laboratory, ASST Spedali Civili di Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Federico","sequence":"additional","affiliation":[{"name":"Clinical Research Development and Phase I Unit, CREA Laboratory, ASST Spedali Civili di Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Todoerti","sequence":"additional","affiliation":[{"name":"Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bachisio","family":"Ziccheddu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnologies and Health Sciences, University of Turin, Turin, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Palermo","sequence":"additional","affiliation":[{"name":"Clinical Research Development and Phase I Unit, CREA Laboratory, ASST Spedali Civili di Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Giacomini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosetta","family":"Ravelli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0328-4673","authenticated-orcid":false,"given":"Federica","family":"Maccarinelli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Belotti","sequence":"additional","affiliation":[{"name":"Hematology, ASST Spedali Civili di Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Ribolla","sequence":"additional","affiliation":[{"name":"Hematology, ASST Spedali Civili di Brescia, Brescia, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6466-7961","authenticated-orcid":false,"given":"Vanessa","family":"Favasuli","sequence":"additional","affiliation":[{"name":"Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy;"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-362X","authenticated-orcid":false,"given":"Alexey S.","family":"Revenko","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Carlsbad, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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