Exploiting KRAS-driven Ferroaddiction in Cancer Through Ferrous Iron-Activatable Drug Conjugates (FeADC)
Ryan K. Muir,
Ryan L Gonciarz,
Adam B Olshen,
Byron C. Hann,
Spencer C Behr,
Michael J Evans,
Posted 14 May 2020
bioRxiv DOI: 10.1101/2020.05.12.088971
Posted 14 May 2020
KRAS mutations cause a quarter of cancer mortality and currently are not sensitive to any targeted, FDA-approved agents. Several inhibitors of the MAPK pathway are FDA approved but exhibit low clinical tolerability at doses needed to adequately extinguish KRAS signaling. We discovered an avidity for ferrous iron (Fe2+) induced by and dependent on oncogenic KRAS signaling. We leveraged an FDA-approved MEK inhibitor to produce a prototypical Ferrous Iron Activatable Drug Conjugate (FeADC) and with this novel agent achieved MAPK blockade in tumor cells while sparing normal tissues. These improvements allowed sustainable, effective treatment of tumor bearing animals with superior tolerability. Iron-activated therapeutics are unknown outside of antiparasitic therapy but may hold significant promise for the treatment of KRAS-driven solid tumors.
- Downloaded 597 times
- Download rankings, all-time:
- Site-wide: 48,596
- In cancer biology: 1,374
- Year to date:
- Site-wide: 26,930
- Since beginning of last month:
- Site-wide: 13,643
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!