ArticleRedox biology2023
Inhibiting SCD expression by IGF1R during lorlatinib therapy sensitizes melanoma to ferroptosis.
Article in Redox biology, 2023. 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, 32 citations in OpenAlex.
- Ferroptosis-associated immune modulation enhances temozolomide efficacy in experimental glioblastoma: potential implications for T-cell infiltration and tumour microenvironment dynamics.Clinical and experimental medicine · 2026Article
- Ferroptosis, pyroptosis, and necroptosis in melanoma: regulatory cell death pathways and their implications for immunotherapy.Frontiers in oncology · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Machine learning-powered discovery of a novel berberine derivative inducing SCD-dependent ferroptosis in osteosarcoma.Journal of translational medicine · 2025Article
- Vorapaxar enhanced mitochondria-associated ferroptosis primes cancer immunotherapy via targeting FOXO1/HMOX1 axis.Cell reports. Medicine · 2025Article
- Specific signaling pathways mediated programmed cell death in tumor microenvironment and target therapies.Discover oncology · 2025Review
- WGCNA and ferroptosis genes in OSCC: unraveling prognostic biomarkers and therapeutic targets.Discover oncology · 2025Article
- Attenuated growth factor signaling during cell death initiation sensitizes membranes towards peroxidation.Nature communications · 2025Article
- Specific Knockdown of the NDUFS4 Gene Reveals Important Roles of Ferroptosis in UVB-induced Photoaging.Inflammation · 2025Article
- Article
- Lapatinib: A Potential Therapeutic Agent for Colon Cancer Targeting Ferroptosis.Anti-cancer agents in medicinal chemistry · 2025Article
- New-Onset Autoantibody-Negative Diabetes With DKA Following Lorlatinib Therapy for ALK-Positive NSCLC.Case reports in endocrinology · 2025Article
- Ferroptosis: mechanisms and therapeutic targets.MedComm · 2024Review
- Propafenone facilitates mitochondrial-associated ferroptosis and synergizes with immunotherapy in melanoma.Journal for immunotherapy of cancer · 2024Article
- Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis.Journal of pharmaceutical analysis · 2024Article
- Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- Integrated analysis and validation of ferroptosis-related genes and immune infiltration in acute myocardial infarction.BMC cardiovascular disorders · 2024Article
- Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer.Frontiers in cell and developmental biology · 2024Review
- Ferroptosis at the nexus of metabolism and metabolic diseases.Theranostics · 2024Review
- Targeting ferroptosis in melanoma: cancer therapeutics.Cell communication and signaling : CCS · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Induction of ferroptosis is an emerging strategy to suppress melanoma progression. Strategies to enhance the sensitivity to ferroptosis induction would be a major advance in melanoma therapy. Here, we used a drug synergy screen that combined a ferroptosis inducer, RSL3, with 240 anti-tumor drugs from the FDA-approved drug library and identified lorlatinib to synergize with RSL3 in melanoma cells. We further demonstrated that lorlatinib sensitized melanoma to ferroptosis through inhibiting PI3K/AKT/mTOR signaling axis and its downstream SCD expression. Moreover, we found that lorlatinib's target IGF1R, but not ALK or ROS1, was the major mediator of lorlatinib-mediated sensitivity to ferroptosis through targeting PI3K/AKT/mTOR signaling axis. Finally, lorlatinib treatment sensitized melanoma to GPX4 inhibition in preclinical animal models, and melanoma patients with low GPX4 and IGF1R expression in their tumors survived for longer period. Altogether, lorlatinib sensitizes melanoma to ferroptosis by targeting IGF1R-mediated PI3K/AKT/mTOR signaling axis, suggesting that combination with lorlatinib could greatly expand the utility of GPX4 inhibition to melanoma patients with IGF1R-proficient expression.
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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.