ArticleThe Journal of experimental medicine2021
Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 49 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- A 3D RNA-protein proximity ligation protocol detecting the heterogeneity of LISRR-RPL26 interactions in patient-derived melanoma tumor explants.STAR protocols · 2026Article
- B7-H6/NKp30 Axis in Melanoma: Translational Rationale, Evidence Gaps, and Therapeutic Considerations.Biomolecules · 2026Review
- Nonsense-mediated mRNA decay: friend or foe in cancer biology?Cell communication and signaling : CCS · 2026Review
- Atypical Tetracyclines Promote Longevity and Ferroptotic Neuroprotection via Translation Attenuation.Aging cell · 2026Article
- Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.The Journal of biological chemistry · 2026Review
- Elevated GCN2 levels in cancer cells confer protection from mitotic stress and faster cell movement.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- AhR-dependent ferroptosis as a therapeutic opportunity to counteract BRAFi-resistance in melanoma.Cell death discovery · 2026Article
- The Janus framework of the integrated stress response: from homeostasis to maladaptation.Life science alliance · 2026Review
- Atypical tetracyclines promote longevity and ferroptotic neuroprotection via translation attenuation.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial proteome landscape unveils key insights into melanoma severity and treatment strategies.Cancer · 2025Article
- RNA G-quadruplexes control mitochondria-localized mRNA translation and energy metabolism.Nature communications · 2025Article
- The long non-coding RNA ROSALIND protects the mitochondrial translational machinery from oxidative damage.Cell death and differentiation · 2025Article
- Review
- Cancer drug-tolerant persister cells: from biological questions to clinical opportunities.Nature reviews. Cancer · 2024Review
- The shaping of mRNA translation plasticity by RNA G-quadruplexes in cancer progression and therapy resistance.NAR cancer · 2024Review
- Development of a chimeric cytokine receptor that captures IL-6 and enhances the antitumor response of CAR-T cells.Cell reports. Medicine · 2024Article
- RNA modifications in physiology and disease: towards clinical applications.Nature reviews. Genetics · 2024Review
- Adaptive changes in tumor cells in response to reductive stress.Biochemical pharmacology · 2024Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to adapt to environmental stress, including therapeutic insult, contributes to tumor evolution and drug resistance. In suboptimal conditions, the integrated stress response (ISR) promotes survival by dampening cytosolic translation. We show that ISR-dependent survival also relies on a concomitant up-regulation of mitochondrial protein synthesis, a vulnerability that can be exploited using mitoribosome-targeting antibiotics. Accordingly, such agents sensitized to MAPK inhibition, thus preventing the development of resistance in BRAFV600E melanoma models. Additionally, this treatment compromised the growth of melanomas that exhibited elevated ISR activity and resistance to both immunotherapy and targeted therapy. In keeping with this, pharmacological inactivation of ISR, or silencing of ATF4, rescued the antitumoral response to the tetracyclines. Moreover, a melanoma patient exposed to doxycycline experienced complete and long-lasting response of a treatment-resistant lesion. Our study indicates that the repurposing of mitoribosome-targeting antibiotics offers a rational salvage strategy for targeted therapy in BRAF mutant melanoma and a therapeutic option for NRAS-driven and immunotherapy-resistant 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.