Targeting ferroptosis in renal cell carcinoma: Potential mechanisms and novel therapeutics

Yang, Lee‐Wei; Fan, Yu; Zhang, Qian

doi:10.1016/j.heliyon.2023.e18504

Cited by 8 publications

(2 citation statements)

References 76 publications

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“…Ferroptosis is the process of cellular accumulation of cytotoxic iron-dependent lipid peroxides that results in programmed cell death, in a manner that is distinct from apoptosis and autophagy, and may be a potential target in mRCC [62]. KD061 is a recently identified molecule that targets iron-sulfur cluster assembly 2 (ISCA2), which is involved in ferroptosis and also decreases HIF-1/2α levels [63].…”

Section: Kd061mentioning

confidence: 99%

Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma

Nguyen,

Oh,

Bahar

et al. 2024

Cancers

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Germline inactivation of the Von Hippel-Lindau (VHL) tumor suppressor is the defining hallmark in hereditary VHL disease and VHL-associated renal cell carcinoma (RCC). However, somatic VHL mutations are also observed in patients with sporadic RCC. Loss of function VHL mutations result in constitutive activation of hypoxia-inducible factor-2 alpha (HIF-2α), which leads to increased expression of HIF target genes that promote angiogenesis and tumor growth. As of 2023, belzutifan is currently the only approved HIF-2α inhibitor for both VHL-associated and sporadic metastatic RCC (mRCC). However, there is potential for resistance with HIF-2α inhibitors which warrants novel HIF-2α-targeting strategies. In this review, we discuss the potential resistance mechanisms with belzutifan and current clinical trials evaluating novel combinations of belzutifan with other targeted therapies and immune checkpoint inhibitors which may enhance the efficacy of HIF-2α targeting. Lastly, we also discuss newer generation HIF-2α inhibitors that are currently under early investigation and outline future directions and challenges with HIF-2α inhibitors for mRCC.

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Section: Kd061mentioning

confidence: 99%

Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma

Nguyen,

Oh,

Bahar

et al. 2024

Cancers

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“…In addition to this, ferroptosis is also being extensively studied in other cancers, including lung cancer, 278 pancreatic cancer, 279 and renal cell carcinoma. 280 Targeting ferroptosis to intervene tumor progression has become a hot topic and focus of research, prospectively providing new therapeutic opportunities for refractory cancers.…”

Section: Ferroptosis In Cancermentioning

confidence: 99%

Endogenous chemicals guard health through inhibiting ferroptotic cell death

Song,

Lei,

et al. 2023

BioFactors

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Ferroptosis is a new form of regulated cell death caused by iron‐dependent accumulation of lethal polyunsaturated phospholipids peroxidation. It has received considerable attention owing to its putative involvement in a wide range of pathophysiological processes such as organ injury, cardiac ischemia/reperfusion, degenerative disease and its prevalence in plants, invertebrates, yeasts, bacteria, and archaea. To counter ferroptosis, living organisms have evolved a myriad of intrinsic efficient defense systems, such as cyst(e)ine‐glutathione‐glutathione peroxidase 4 system (cyst(e)ine‐GPX4 system), guanosine triphosphate cyclohydrolase 1/tetrahydrobiopterin (BH4) system (GCH1/BH4 system), ferroptosis suppressor protein 1/coenzyme Q10 system (FSP1/CoQ10 system), and so forth. Among these, GPX4 serves as the only enzymatic protection system through the reduction of lipid hydroperoxides, while other defense systems ultimately rely on small compounds to scavenge lipid radicals and prevent ferroptotic cell death. In this article, we systematically summarize the chemical biology of lipid radical trapping process by endogenous chemicals, such as coenzyme Q10 (CoQ10), BH4, hydropersulfides, vitamin K, vitamin E, 7‐dehydrocholesterol, with the aim of guiding the discovery of novel ferroptosis inhibitors.

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Sodium Selenite Prevents Matrine-Induced Nephrotoxicity by Suppressing Ferroptosis via the GSH-GPX4 Antioxidant System

Wang,

Lin,

et al. 2024

Biol Trace Elem Res

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Targeting ferroptosis in renal cell carcinoma: Potential mechanisms and novel therapeutics

Cited by 8 publications

References 76 publications

Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma

Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma

Endogenous chemicals guard health through inhibiting ferroptotic cell death

Sodium Selenite Prevents Matrine-Induced Nephrotoxicity by Suppressing Ferroptosis via the GSH-GPX4 Antioxidant System

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