Erratum: Corrigendum: Modulating the therapeutic response of tumours to dietary serine and glycine starvation

Maddocks, Oliver D.K.; Athineos, Dimitris; Cheung, Eric C.; Lee, Pearl; Zhang, Tong; Broek, Niels J. F. van den; Mackay, Gillian; Gay, David; Kruiswijk, Flore; Blagih, Julianna; Vincent, David F.; Campbell, Kirsteen J.; Ceteci, Fatih; Sansom, Owen J.; Blyth, Karen; Vousden, Karen H.

doi:10.1038/nature23471

Cited by 10 publications

(9 citation statements)

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“…In genetically engineered mouse models of serine-dependent tumors, such as Myc-driven lymphoma and inactive-Apc-driven intestinal tumors, the administration of a serine and glycine (SG)-free diet reduces tumor growth. Noteworthy, the efficacy of SG deprivation is strongly dependent on the genetic alterations of tumors, as demonstrated by the limited efficacy of SG starvation in affecting the survival of mice harboring PDAC cells induced to express activated KRAS, which are able to respond to dietary SG restriction by upregulating SSP [99]. In addition, in mice harboring colon xenograft tumors, SG dietary restriction also promotes the accumulation of toxic deoxysphingolipids and mitigates tumor growth, an effect that can be further potentiated by inhibiting PHGDH [100].…”

Section: Modulation Of Amino Acid Availability For Cancer Therapymentioning

confidence: 99%

Metabolic Reprogramming in Anticancer Drug Resistance: A Focus on Amino Acids

et al. 2021

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Overcoming anticancer drug resistance is a major challenge in cancer therapy, requiring innovative strategies that consider the great tumor heterogeneity and adaptability. Here we provide recent evidence highlighting the key role of amino acid (AA) metabolic reprogramming in cancer cells and the supportive microenvironment in driving resistance to anticancer therapies. AAs sustain the acquisition of anticancer resistance by providing essential building blocks for biosynthetic pathways and for maintaining a balanced redox status, and modulating the epigenetic profile of both malignant and non-malignant cells. Besides, AAs also support the reduced intrinsic susceptibility of cancer stem cells to antineoplastic therapies. These findings shed new light on the possibility of targeting non-responding tumors by modulating AAs availability, through pharmacological approaches or dietary interventions.

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Section: Modulation Of Amino Acid Availability For Cancer Therapymentioning

confidence: 99%

Metabolic Reprogramming in Anticancer Drug Resistance: A Focus on Amino Acids

et al. 2021

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“…Besides protein biosynthesis, serine represents a building block for sphingolipid synthesis and its catabolism provides essential building blocks for nucleotides synthesis. Consequently, serine/glycine (S/G) starvation has gained much attention as a dietary anticancer intervention (41). Alternative to anabolic needs, catabolism of serine via the mitochondrial folate pathway can also give rise to net production of ATP (42).…”

Section: Resultsmentioning

confidence: 99%

Metabolic plasticity of serine metabolism is crucial for cGAS/STING-signalling and innate immune response to viral infections in the gut

Wottawa

Becker

Bakr

et al. 2022

Preprint

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Mucosal cytomegalovirus (CMV) infection represents a leading cause for complicated disease behaviour and proctocolectomy in patients with inflammatory bowel disease (IBD). Using a genetic loss-of-function mouse model of the hypomorphic IBD risk gene X-box-binding protein 1 (XBP1), isotope-assisted metabolomics and pharmacologic approaches, we unravel the molecular control of gut epithelial STING signalling by unresolved endoplasmic reticulum (ER) stress. We demonstrate that unresolved epithelial ER stress, evoked by Xbp1 deficiency, leads to exhausted STING signalling and an impaired ability to control CMV infection, which is driven by the generation of reactive oxygen species (ROS). ROS generation is controlled by cellular glycine influx and de-novo serin synthesis enabling glutathione production, which can be pharmacologically exploited to restrore STING signaling. Pharmacological scavenging of ROS with N-acetly cysteine restores epithelial STING signalling and limits CMV infection in IECs. Our findings unravel the serine-glycine dependent metabolic control by ER stress that licences STING signaling and susceptibility to infection in gut epithelium.

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“…However, it remains unknown whether methionine dependence is a broader feature across pediatric cancers and whether this dependency can be effectively exploited against tumors in children. Besides methionine, serine deprivation has also been shown to induce oxidative stress and prohibit tumor growth in adult cancer models (125,126). Given that NB and ES showed active serine metabolism (49,73), it will be interesting to determine whether serine restriction is effective in treating those cancers.…”

Section: Nutrient Restrictionmentioning

confidence: 99%

The opportunities and challenges for nutritional intervention in childhood cancers

et al. 2023

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Diet dictates nutrient availability in the tumor microenvironment, thus affecting tumor metabolic activity and growth. Intrinsically, tumors develop unique metabolic features and are sensitive to environmental nutrient concentrations. Tumor-driven nutrient dependencies provide opportunities to control tumor growth by nutritional restriction or supplementation. This review summarized the existing data on nutrition and pediatric cancers after systematically searching articles up to 2023 from four databases (PubMed, Web of Science, Scopus, and Ovid MEDLINE). Epidemiological studies linked malnutrition with advanced disease stages and poor clinical outcomes in pediatric cancer patients. Experimental studies identified several nutrient dependencies (i.e., amino acids, lipids, vitamins, etc.) in major pediatric cancer types. Dietary modifications such as calorie restriction, ketogenic diet, and nutrient restriction/supplementation supported pediatric cancer treatment, but studies remain limited. Future research should expand epidemiological studies through data sharing and multi-institutional collaborations and continue to discover critical and novel nutrient dependencies to find optimal nutritional approaches for pediatric cancer patients.

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Erratum: Corrigendum: Modulating the therapeutic response of tumours to dietary serine and glycine starvation

Cited by 10 publications

References 1 publication

Metabolic Reprogramming in Anticancer Drug Resistance: A Focus on Amino Acids

Metabolic Reprogramming in Anticancer Drug Resistance: A Focus on Amino Acids

Metabolic plasticity of serine metabolism is crucial for cGAS/STING-signalling and innate immune response to viral infections in the gut

The opportunities and challenges for nutritional intervention in childhood cancers

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