ArticleThe Journal of experimental medicine2022
Ferrous iron-activatable drug conjugate achieves potent MAPK blockade in KRAS-driven tumors.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Intracellular Activation of Dual-Pharmacophore Artezomib Enhances Selective Cytotoxicity in Hematologic Malignancies.Journal of medicinal chemistry · 2026Article
- Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- PI5P4Kα promotes glucose and iron acquisition to support metabolic fitness in pancreatic cancer.Cell reports · 2025Article
- Thioredoxin Reductase 1 inhibition triggers ferroptosis in KRAS-independent lung cancers.bioRxiv : the preprint server for biology · 2025Article
- FTO facilitates colorectal cancer chemoresistance via regulation of NUPR1-dependent iron homeostasis.Redox biology · 2025Article
- Genetics and biology of pancreatic ductal adenocarcinoma.Genes & development · 2025Review
- Association between serum iron status and the risk of colorectal cancer in US adults: a cross-sectional analysis of NHANES 2001-2020.BMC gastroenterology · 2024Article
- The research advances in Kirsten rat sarcoma viral oncogene homolog (KRAS)-related cancer during 2013 to 2022: a scientometric analysis.Frontiers in oncology · 2024Article
- In vivo bioluminescence imaging of labile iron in xenograft models and liver using FeAL-1, an iron-activatable form of D-luciferin.Cell chemical biology · 2023Article
- Drug-tolerant persister cells in cancer: the cutting edges and future directions.Nature reviews. Clinical oncology · 2023Review
- A Neurosurgical Perspective on Brain Metastases from Renal Cell Carcinoma: Multi-Institutional, Retrospective Analysis.Biomedicines · 2023Article
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Uptake of H-ferritin by Glioblastoma stem cells and its impact on their invasion capacity.Journal of cancer research and clinical oncology · 2023Article
- Temporal modelling of the biofilm lifecycle (TMBL) establishes kinetic analysis of plate-based bacterial biofilm dynamics.Journal of microbiological methods · 2023Article
- Review
- Elevated labile iron in castration-resistant prostate cancer is targetable with ferrous iron-activatable antiandrogen therapy.European journal of medicinal chemistry · 2023Article
- Exploring KRAS-mutant pancreatic ductal adenocarcinoma: a model validation study.Frontiers in immunology · 2023Article
- NCOA4-Mediated Ferritinophagy Is a Pancreatic Cancer Dependency via Maintenance of Iron Bioavailability for Iron-Sulfur Cluster Proteins.Cancer discovery · 2022Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
KRAS mutations drive a quarter of cancer mortality, and most are undruggable. Several inhibitors of the MAPK pathway are FDA approved but poorly tolerated at the doses needed to adequately extinguish RAS/RAF/MAPK signaling in the tumor cell. We found that oncogenic KRAS signaling induced ferrous iron (Fe2+) accumulation early in and throughout mutant KRAS-mediated transformation. We converted an FDA-approved MEK inhibitor into a ferrous iron-activatable drug conjugate (FeADC) and achieved potent MAPK blockade in tumor cells while sparing normal tissues. This innovation allowed sustainable, effective treatment of tumor-bearing animals, with tumor-selective drug activation, producing superior systemic tolerability. Ferrous iron accumulation is an exploitable feature of KRAS transformation, and FeADCs hold promise for improving the treatment of KRAS-driven solid tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.