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Kathryn M. Lemberg, … , Rana Rais, Barbara S. Slusher
Published January 4, 2022
Citation Information: J Clin Invest. 2022;132(1):e148550. https://doi.org/10.1172/JCI148550.
Citation Information: J Clin Invest. 2022;132(1):e148550. https://doi.org/10.1172/JCI148550.
Abstract
Metabolic inhibitors have been used in oncology for decades, dating back to antimetabolites developed in the 1940s. In the past 25 years, there has been increased recognition of metabolic derangements in tumor cells leading to a resurgence of interest in targeting metabolism. More recently there has been recognition that drugs targeting tumor metabolism also affect the often acidic, hypoxic, immunosuppressive tumor microenvironment (TME) and non-tumor cell populations within it, including immune cells. Here we review small-molecule metabolic inhibitors currently in clinical development for oncology applications. For each agent, we evaluate the preclinical studies demonstrating antitumor and TME effects and review ongoing clinical trials. The goal of this Review is to provide an overview of the landscape of metabolic inhibitors in clinical development for oncology.
Authors
Kathryn M. Lemberg, Sadakatali S. Gori, Takashi Tsukamoto, Rana Rais, Barbara S. Slusher
Citation information
Citations to this article (69)
| Title and authors | Publication | Year |
|---|---|---|
|
A Pilot Study of Exosome Proteomic Profiling Reveals Dysregulated Metabolic Pathways in Endometrial Cancer
Kharrat F, Capaci V, Conti A, Golino V, Campiglia P, Balasan N, Aloisio M, Licastro D, Monasta L, Caponneto F, Beltrami AP, Romano F, di Lorenzo G, Ricci G, Ura B |
Biomedicines | 2025 |
|
Artificial metabzyme‐driven metabolic reprogramming and precision oncology
Hu X, Ling D |
Clinical and Translational Medicine | 2025 |
|
Megakaryocytes transfer mitochondria to bone marrow mesenchymal stromal cells to lower platelet activation
Chengjie Gao, Yitian Dai, Paul A. Spezza, Paul Boasiako, Alice Tang, Giselle Rasquinha, Hui zhong, Bojing Shao, Yunfeng Liu, Patricia A Shi, Cheryl A. Lobo, Xiuli An, Anqi Guo, William B. Mitchell, Deepa Manwani, Karina Yazdanbakhsh, Avital Mendelson |
Journal of Clinical Investigation | 2025 |
|
Metabolic Heterogeneity in Diffuse Large B-Cell Lymphoma Cells Reveals an Innovative Antimetabolic Combination Strategy
Lordello L, Nuan-Aliman S, Kielbassa-Elkadi K, Montagne A, Kotta K, Martins I, Pinto Jurado E, Caradeuc C, Lehmann-Che J, Martínez-Climent JÁ, Meignin V, Giraud N, Kroemer G, Bertho G, Thieblemont C, Baud V |
Cancers | 2025 |
|
Cooperative Hedgehog/GLI and JAK/STAT signaling drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer
Elmer DP, Stockmaier G, Grund-Gröschke S, Strobl V, Dang HH, Wiederstein M, Licha D, Strobl A, Eglseer A, Sternberg C, Tesanovic S, Gruber W, Wolff F, Moriggl R, Risch A, Reischl R, Huber CG, Krenn PW, Fortelny N, Horejs-Hoeck J, Aberger F |
Cell Communication and Signaling : CCS | 2025 |
|
Targeting amino acid metabolism to inhibit gastric cancer progression and promote anti-tumor immunity: a review
Jiang Y, Tao Q, Qiao X, Yang Y, Peng C, Han M, Dong K, Zhang W, Xu M, Wang D, Zhu W, Li X |
Frontiers in Immunology | 2025 |
|
Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance
Suri C, Pande B, Suhasini Sahithi L, Swarnkar S, Khelkar T, Verma HK |
Cancer Drug Resistance | 2025 |
|
Metabolomic Profiling of Disease Progression Following Radiotherapy for Breast Cancer
McMahon AN, Reis IM, Takita C, Wright JL, Hu JJ |
Cancers | 2025 |
|
Recent Advances and Challenges in the Treatment of Advanced Pancreatic Cancer: An Update on Completed and Ongoing Clinical Trials
Shenoy A, Yousif A, Hussain MD |
Cancers | 2025 |
|
Mitochondrial reprogramming by activation of oxidative phosphorylation via glutamine metabolism in bladder tumors of african american patients
Karthik Reddy, Danthasinghe Piyarathna, JunHyoung Park, Vasanta Putluri, Chandra Amara, Jianjun Gao, Roni Bollag, Martha Terris, Yair Lotan, Seth Lerner, Arun Sreekumar, Benny Kaipparettu, Nagireddy Putluri |
JCI Insight | 2024 |
|
From Machine Learning to Patient Outcomes: A Comprehensive Review of AI in Pancreatic Cancer
Tripathi S, Tabari A, Mansur A, Dabbara H, Bridge CP, Daye D |
Diagnostics | 2024 |
|
Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology
Menendez JA, Cuyàs E, Encinar JA, Vander Steen T, Verdura S, Llop\u2010Hernández À, López J, Serrano\u2010Hervás E, Osuna S, Martin\u2010Castillo B, Lupu R |
Molecular Oncology | 2024 |
|
Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma
Gao J, Wang J, Guan C, Shi W, Dong Q, Sheng J, Zou X, Xu Z, Ge Y, Huang Z, Li J, Bao H, Xu Y, Cui Y, Xu X, Zhong X |
Journal of Cancer | 2024 |
|
Canonical and non-canonical roles of complement in atherosclerosis.
Maffia P, Mauro C, Case A, Kemper C |
Nature reviews. Cardiology | 2024 |
|
Combinatorial strategies to target RAS-driven cancers.
Perurena N, Situ L, Cichowski K |
Nature reviews. Cancer | 2024 |
|
Bisbiguanide analogs induce mitochondrial stress to inhibit lung cancer cell invasion
Knippler CM, Arnst JL, Robinson IE, Matsuk V, Khatib TO, Harvey RD, Shanmugam M, Mouw JK, Fu H, Ganesh T, Marcus AI |
iScience | 2024 |
|
Cancer cell metabolism and antitumour immunity.
De Martino M, Rathmell JC, Galluzzi L, Vanpouille-Box C |
Nature reviews. Immunology | 2024 |
|
IκBα kinase inhibitor BAY 11-7082 promotes anti-tumor effect in RAS-driven cancers
Guruvaiah P, Gupta R |
Journal of Translational Medicine | 2024 |
|
Exploring treatment options in cancer: Tumor treatment strategies
Liu B, Zhou H, Tan L, Siu KT, Guan XY |
Signal Transduction and Targeted Therapy | 2024 |
|
Inverse FASN and LDHA correlation drives metabolic resistance in breast cancer
Papulino C, Chianese U, Ali A, Favale G, Tuccillo C, Ciardiello F, Di Mauro A, Mignogna C, Ferrara G, Budillon A, Megchelenbrink WL, Del Gaudio N, Conte M, Merciai F, Campiglia P, Altucci L, Carafa V, Sommella E, Benedetti R |
Journal of Translational Medicine | 2024 |
|
Metabolic reprogramming of the tumor microenvironment to enhance immunotherapy
Lim SA |
BMB Reports | 2024 |
|
Development of a Competitive Nutrient-Based T-Cell Immunotherapy Designed to Block the Adaptive Warburg Effect in Acute Myeloid Leukemia.
Cao H, Xiao J, Baylink DJ, Nguyen V, Shim N, Lee J, Mallari DJR, Wasnik S, Mirshahidi S, Chen CS, Abdel-Azim H, Reeves ME, Xu Y |
Biomedicines | 2024 |
|
Regulatory T cells in immune checkpoint blockade antitumor therapy
Zhang A, Fan T, Liu Y, Yu G, Li C, Jiang Z |
Molecular Cancer | 2024 |
|
Reactive oxygen species induced by SARS-CoV-2 infection can induce EMT in solid tumors: Potential role of COVID-19 in chemo-resistance and metastasis
Moulaeian M, Ferdousmakan S, Banihashemi S, Homayounfar S, Pasupulla AP, Malekzadegan Y |
Heliyon | 2024 |
|
SOCS1 Inhibits IL-6-Induced CD155 Overexpression in Lung Adenocarcinoma
Marroquin-Muciño M, Benito-Lopez JJ, Perez-Medina M, Aguilar-Cazares D, Galicia-Velasco M, Chavez-Dominguez R, Meza-Toledo SE, Meneses-Flores M, Camarena A, Lopez-Gonzalez JS |
International Journal of Molecular Sciences | 2024 |
|
Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma
Duraj T, Kalamian M, Zuccoli G, Maroon JC, D\u2019Agostino DP, Scheck AC, Poff A, Winter SF, Hu J, Klement RJ, Hickson A, Lee DC, Cooper I, Kofler B, Schwartz KA, Phillips MC, Champ CE, Zupec-Kania B, Tan-Shalaby J, Serfaty FM, Omene E, Arismendi-Morillo G, Kiebish M, Cheng R, El-Sakka AM, Pflueger A, Mathews EH, Worden D, Shi H, Cincione RI, Spinosa JP, Slocum AK, Iyikesici MS, Yanagisawa A, Pilkington GJ, Chaffee A, Abdel-Hadi W, Elsamman AK, Klein P, Hagihara K, Clemens Z, Yu GW, Evangeliou AE, Nathan JK, Smith K, Fortin D, Dietrich J, Mukherjee P, Seyfried TN |
BMC Medicine | 2024 |
|
Oncometabolites in pancreatic cancer: Strategies and its implications
Maiti A, Mondal S, Choudhury S, Bandopadhyay A, Mukherjee S, Sikdar N |
World Journal of Experimental Medicine | 2024 |
|
Momordicine-I suppresses head and neck cancer growth by modulating key metabolic pathways
Bandyopadhyay D, Tran ET, Patel RA, Luetzen MA, Cho K, Shriver LP, Patti GJ, Varvares MA, Ford DA, McCommis KS, Ray RB |
Cell Communication and Signaling : CCS | 2024 |
|
Challenges in Metabolite Biomarkers as Avenues of Diagnosis and Prognosis of Cancer
Sharma NK, Sarode SC, Sekar G, Sonawane K, Bomle D |
Journal of Cancer Prevention | 2024 |
|
Fuel for thought: targeting metabolism in lung cancer
Schneider JL, Han S, Nabel CS |
Translational Lung Cancer Research | 2024 |
|
Role of myeloid-derived suppressor cells in tumor recurrence
Cole K, Al-Kadhimi Z, Talmadge JE |
Cancer metastasis reviews | 2023 |
|
FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma
Chianese U, Papulino C, Ali A, Ciardiello F, Cappabianca S, Altucci L, Carafa V, Benedetti R |
Journal of Translational Medicine | 2023 |
|
Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment
Benito-Lopez JJ, Marroquin-Muciño M, Perez-Medina M, Chavez-Dominguez R, Aguilar-Cazares D, Galicia-Velasco M, Lopez-Gonzalez JS |
Frontiers in Oncology | 2023 |
|
Modulating Glycolysis to Improve Cancer Therapy
Chelakkot C, Chelakkot VS, Shin Y, Song K |
International journal of molecular sciences | 2023 |
|
NRF2 activation induces NADH-reductive stress providing a metabolic vulnerability in lung cancer
Weiss-Sadan T, Ge M, Hayashi M, Gohar M, Yao CH, de Groot A, Harry S, Carlin A, Fischer H, Shi L, Wei TY, Adelmann CH, Wolf K, Vornbäumen T, Dürr BR, Takahashi M, Richter M, Zhang J, Yang TY, Vijay V, Fisher DE, Hata AN, Haigis MC, Mostoslavsky R, Bardeesy N, Papaginanakopoulos T, Bar-Peled L |
Cell Metabolism | 2023 |
|
Involvement of the pro-oncogenic enzyme fatty acid synthase in the hallmarks of cancer: a promising target in anti-cancer therapies
Vanauberg D, Schulz C, Lefebvre T |
Oncogenesis | 2023 |
|
Pancreatic Cancer: Advances and Challenges
Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A |
Cell | 2023 |
|
PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress
Yoon BK, Kim H, Oh TG, Oh SK, Jo S, Kim M, Chun KH, Hwang N, Lee S, Jin S, Atkins AR, Yu RT, Downes M, Kim JW, Kim H, Evans RM, Cheong JH, Fang S |
Proceedings of the National Academy of Sciences | 2023 |
|
Targeting Oncometabolites in Peritoneal Cancers: Preclinical Insights and Therapeutic Strategies
Nadhan R, Kashyap S, Ha JH, Jayaraman M, Song YS, Isidoro C, Dhanasekaran DN |
Metabolites | 2023 |
|
Amino Acid Metabolism in Bone Metastatic Disease.
Edwards DN |
Current Osteoporosis Reports | 2023 |
|
Rethinking our approach to cancer metabolism to deliver patient benefit.
Tardito S, MacKay C |
British Journal of Cancer | 2023 |
|
Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis
Chaudagar K, Hieromnimon HM, Kelley A, Labadie B, Shafran J, Rameshbabu S, Drovetsky C, Bynoe K, Solanki A, Markiewicz E, Fan X, Loda M, Patnaik A |
2023 | |
|
Breast cancers as ecosystems: a metabolic perspective
Martino F, Lupi M, Giraudo E, Lanzetti L |
Cellular and Molecular Life Sciences | 2023 |
|
Glutamine metabolic reprogramming in hepatocellular carcinoma
Ye Y, Yu B, Wang H, Yi F |
Frontiers in Molecular Biosciences | 2023 |
|
Glycolysis-related biomarker TCIRG1 participates in regulation of renal cell carcinoma progression and tumor immune microenvironment by affecting aerobic glycolysis and AKT/mTOR signaling pathway.
Di S, Gong M, Lv J, Yang Q, Sun Y, Tian Y, Qian C, Chen W, Zhou W, Dong K, Shi X, Wang Y, Wang H, Chu J, Gan S, Pan X, Cui X |
Cancer Cell International | 2023 |
|
Integrative analysis of mitochondrial metabolic reprogramming in early-stage colon and liver cancer
Kim Y, Shin SY, Jeung J, Kim Y, Kang YW, Lee S, Oh CM |
Frontiers in Oncology | 2023 |
|
Differential effects of glutamine inhibition strategies on anti-tumor CD8 T cells
Madden MZ, Ye X, Chi C, Fisher EL, Wolf MM, Needle GA, Bader JE, Patterson AR, Reinfeld BI, Landis MD, Hathaway ES, Muka JE, O\u2019Neil RT, Karijolich J, Philip M, Rathmell JC |
Journal of immunology (Baltimore, Md. : 1950) | 2023 |
|
Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma
Tsuchimochi S, Wada-Hiraike O, Urano Y, Kukita A, Yamaguchi K, Honjo H, Taguchi A, Tanikawa M, Sone K, Mori-Uchino M, Tsuruga T, Oda K, Osuga Y |
Scientific Reports | 2023 |
|
Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma
Ramesh V, Gollavilli PN, Pinna L, Siddiqui MA, Turtos AM, Napoli F, Antonelli Y, Leal\u2010Egaña A, Havelund JF, Jakobsen ST, Boiteux EL, Volante M, Færgeman NJ, Jensen ON, Siersbæk R, Somyajit K, Ceppi P |
EMBO Molecular Medicine | 2023 |
|
Natural Products Induce Different Anti-Tumor Immune Responses in Murine Models of 4T1 Mammary Carcinoma and B16-F10 Melanoma
Lasso P, Rojas L, Arévalo C, Urueña C, Murillo N, Fiorentino S |
International journal of molecular sciences | 2023 |
|
Suppression of Tumor Cell Lactate-generating Signaling Pathways Eradicates Murine PTEN/p53-deficient Aggressive-variant Prostate Cancer via Macrophage Phagocytosis.
Chaudagar K, Hieromnimon HM, Kelley A, Labadie B, Shafran J, Rameshbabu S, Drovetsky C, Bynoe K, Solanki A, Markiewicz E, Fan X, Loda M, Patnaik A |
Clinical cancer research | 2023 |
|
Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non-small cell lung cancer
Wenjun Mao, Yun Cai, Danrong Chen, Guanyu Jiang, Yongrui Xu, Ruo Chen, Fengxu Wang, Xuehai Wang, Mingfeng Zheng, Xinyuan Zhao, Jie Mei |
JCI Insight | 2022 |
|
Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours
Weber V, Arnaud L, Dukic-Stefanovic S, Wenzel B, Roux V, Chezal JM, Lai TH, Teodoro R, Kopka K, Miot-Noirault E, Deuther-Conrad W, Maisonial-Besset A |
Molecules (Basel, Switzerland) | 2022 |
|
Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance
Vasseur S, Guillaumond F |
Oncogenesis | 2022 |
|
Metabolic cross-talk within the bone marrow milieu: focus on multiple myeloma.
Oudaert I, Van der Vreken A, Maes A, De Bruyne E, De Veirman K, Vanderkerken K, Menu E |
Experimental Hematology and Oncology | 2022 |
|
The exploitation of enzyme-based cancer immunotherapy.
Chandan G, Saini AK, Kumari R, Chakrabarti S, Mittal A, Sharma AK, Saini RV |
Human Cell | 2022 |
|
Pathological implications of metabolic reprogramming and its therapeutic potential in medulloblastoma.
Marabitti V, Giansanti M, De Mitri F, Gatto F, Mastronuzzi A, Nazio F |
Frontiers in Cell and Developmental Biology | 2022 |
|
Metabolic Plasticity of Cancer Stem Cells in Response to Microenvironmental Cues.
Xie Y, Ma S, Tong M |
Cancers | 2022 |
|
Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer.
Choi SYC, Ribeiro CF, Wang Y, Loda M, Plymate SR, Uo T |
Biomolecules | 2022 |
|
2-Deoxyglucose, an Inhibitor of Glycolysis, Enhances the Oncolytic Effect of Coxsackievirus
Vorobyev PO, Kochetkov DV, Chumakov PM, Zakirova NF, Zotova-Nefedorova SI, Vasilenko KV, Alekseeva ON, Kochetkov SN, Bartosch B, Lipatova AV, Ivanov AV |
Cancers | 2022 |
|
Advances in Understanding of Metabolism of B-Cell Lymphoma: Implications for Therapy
Kluckova K, D\u2019Avola A, Riches JC |
Cancers | 2022 |
|
Discovery of DRP-104, a tumor-targeted metabolic inhibitor prodrug
Rais R, Lemberg KM, Tenora L, Arwood ML, Pal A, Alt J, Wu Y, Lam J, Aguilar JM, Zhao L, Peters DE, Tallon C, Pandey R, Thomas AG, Dash RP, Seiwert T, Majer P, Leone RD, Powell JD, Slusher BS |
Science Advances | 2022 |
|
Glutamine metabolism and radiosensitivity: Beyond the Warburg effect
Alden RS, Kamran MZ, Bashjawish BA, Simone BA |
Frontiers in Oncology | 2022 |
|
Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications
Wu Y, Chen W, Guo M, Tan Q, Zhou E, Deng J, Li M, Chen J, Yang Z, Jin Y |
International Journal of Nanomedicine | 2022 |
|
Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?
Tannoury M, Garnier D, Susin SA, Bauvois B |
Cancers | 2022 |
|
Importance of lactate dehydrogenase (LDH) and monocarboxylate transporters (MCTs) in cancer cells
Hatami H, Sajedi A, Mir SM, Memar MY |
2022 | |
|
Effects of metabolic cancer therapy on tumor microenvironment
Hyroššová P, Milošević M, Škoda J, Vachtenheim Jr J, Rohlena J, Rohlenová K |
Frontiers in Oncology | 2022 |
|
Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics
Pal S, Sharma A, Mathew SP, Jaganathan BG |
Frontiers in immunology | 2022 |
|
Applying HT-SAXS to chemical ligand screening
Brosey CA, Shen R, Moiani D, Jones DE, Burnett K, Hura GL, Tainer JA |
Methods in enzymology | 2022 |
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