Oliver Mortusewicz

Amazing work and truly inspiring!

New @nature.com
An ingenious way to track DNA replication patterns at the single-cell level that leads to cell heterogeneity and daughter cells that can potentially give rise to cancer
www.nature.com/articles/s41...

Huge thanks to James Haslam, Helge Gad and Thomas Helleday! A special thanks also to the Molecular Cell @cp-molcell.bsky.social editorial team and the Reviewers for their invaluable feedback.

🔬 We discuss:
- The origins of uracil in DNA and the cellular machinery dedicated to its repair.
- The intricate ways uracil-induced replication stress compromises genome integrity.
- Implications for designing and improving anti-cancer therapies, particularly those targeting nucleotide metabolism.

🚀 Thrilled to share our latest review: "Uracil-induced replication stress drives mutations, genome instability, anti-cancer treatment efficacy, and resistance"

👉 doi.org/10.1016/j.mo...

#CancerResearch #DNARepair #ReplicationStress #MolecularCell #GenomicInstability #CancerTherapy #Uracil

Conventional chemotherapy: millions of cures, unresolved therapeutic index Article abstract In recent decades, millions of patients with cancer have been cured by chemotherapy alone. By ‘cure’, we mean that patients with cancers that would be fatal if left untreated receive a time-limited course of chemotherapy and their cancer disappears, never to return. In an era when hundreds of thousands of cancer genomes have been sequenced, a remarkable fact persists: in most patients who have been cured, we still do not fully understand the mechanisms underlying the therapeutic index by which the tumour cells are killed, but normal cells are somehow spared. In contrast, in more recent years, patients with cancer have benefited from targeted therapies that usually do not cure but whose mechanisms of therapeutic index are, at least superficially, understood. In this Perspective, we will explore the various and sometimes contradictory models that have attempted to explain why chemotherapy can cure some patients with cancer, and what gaps in our understanding of the therapeutic index of chemotherapy remain to be filled. We will summarize principles which have benefited curative conventional chemotherapy regimens in the past, principles which might be deployed in constructing combinations that include modern targeted therapies.

Great perspective on the importance of conventional chemotherapy.

Despite many many decades of successful use, do we understand how these drugs work?

www.nature.com/articles/s41...

Cancer Research KI (CRKI) on LinkedIn: Blue Sky Research Grant Recipients Cancer Research KI (CRKI) would like to congratulate the ten recipients of the Blue Sky Grant for innovative cancer research in 2024: Kutter Claudia Erdinc…

www.linkedin.com/posts/cancer...

Thanks again for the support @CRKI!

Chromosomal instability as a driver of cancer progression - Nature Reviews Genetics Chromosomal instability (CIN) drives cancer progression through diverse mechanisms. The authors review the molecular consequences of CIN in advanced cancer, such as genomic and phenotypic heterogeneit...

www.nature.com/articles/s41...

Thanks a lot Kumar! 🙏

Very happy to have been able to contribute to this amazing story! Check out the paper at Nature Communications and the 🧵 by @nckvalerie.bsky.social below 👇. We believe #CeTeam will be an invaluable tool for #drugdiscovery and #targetvalidation in #cells

🔗: www.nature.com/articles/s41...

Couldn't have wished for a better first post here. I’m very happy and grateful to have received a #BlueSkyGrant from #KarolinskaInstitutet. This will allow us to validate the DNA Glycosylase #SMUG1 as a #target to exploit uracil toxicity in combination #therapy for colorectal #cancer.