ArticleCancer research2025
De Novo Serine Synthesis Is a Metabolic Vulnerability That Can Be Exploited to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- Article
- HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- Mitochondrial Dysfunction in Renal Cell Carcinoma: A Comprehensive Review of Pathogenic Mechanisms and Emerging Therapeutic Opportunities.Oncology research · 2026Review
- Bioinformatics-based discovery of the involvement of PSAT1 in mediating the anti-lung adenocarcinoma activity of triptolide.Animal models and experimental medicine · 2026Article
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Sunitinib is an oral tyrosine kinase inhibitor used in treating advanced renal cell carcinoma (RCC) that exhibits significant efficacy but faces resistance in 30% of patients. Identifying the molecular mechanisms underlying resistance could enable the development of strategies to enhance sunitinib sensitivity. In this study, we showed that sunitinib induces a metabolic shift leading to increased serine synthesis in RCC cells. Activation of the GCN2-ATF4 stress response pathway was identified as the mechanistic link between sunitinib treatment and elevated serine production. The increased serine biosynthesis supported nucleotide synthesis and sustained cell proliferation, migration, and invasion following sunitinib treatment. Inhibiting key enzymes in the serine synthesis pathway, such as phosphoglycerate dehydrogenase and phosphoserine aminotransferase 1, enhanced the sensitivity of resistant cells to sunitinib. Beyond RCC, similar activation of serine synthesis following sunitinib treatment occurred in a variety of other cancer types, suggesting a shared adaptive response to sunitinib therapy. Together, this study identifies the de novo serine synthesis pathway as a potential target to overcome sunitinib resistance, offering insights into therapeutic strategies applicable across diverse cancer contexts. Significance: Sunitinib treatment induces metabolic reprogramming to provide essential metabolite building blocks for tumor survival, resistance, and progression by upregulating serine biosynthesis, which represents a targetable dependency to enhance therapeutic efficacy.
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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.