Journal ArticleDOI
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond
Michael Platten,Michael Platten,Ellen A. A. Nollen,Ute F. Röhrig,Francesca Fallarino,Christiane A. Opitz +5 more
TLDR
An overview of the physiological and pathophysiological roles of tryptophan metabolism is provided, focusing on the clinical potential and challenges associated with targeting this pathway.Abstract:
L-Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is involved in the regulation of immunity, neuronal function and intestinal homeostasis. Imbalances in Trp metabolism in disorders ranging from cancer to neurodegenerative disease have stimulated interest in therapeutically targeting the KP, particularly the main rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan-2,3-dioxygenase (TDO) as well as kynurenine monooxygenase (KMO). However, although small-molecule IDO1 inhibitors showed promise in early-stage cancer immunotherapy clinical trials, a phase III trial was negative. This Review summarizes the physiological and pathophysiological roles of Trp metabolism, highlighting the vast opportunities and challenges for drug development in multiple diseases.read more
Citations
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Immunity to Fungal Infections
TL;DR: The nature and function of the immune response to fungi is an exciting challenge that might set the stage for new approaches to the treatment of fungal diseases, from immunotherapy to vaccines.
Journal ArticleDOI
Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity.
TL;DR: In this paper, the major genomic and metabolic characteristics of myeloid-derived suppressor cells (MDSCs) are discussed and how these characteristics shape MDSC function and could facilitate therapeutic targeting of these cells particularly in cancer and in autoimmune diseases.
Journal ArticleDOI
Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions
Patrick Y. Wen,Michael Weller,Eudocia Q. Lee,Brian M. Alexander,Jill S. Barnholtz-Sloan,Floris P. Barthel,Tracy T. Batchelor,Ranjit S. Bindra,Susan M. Chang,E. Antonio Chiocca,Timothy F. Cloughesy,John DeGroot,Evanthia Galanis,Mark R. Gilbert,Monika E. Hegi,Craig Horbinski,Raymond Y. Huang,Andrew B. Lassman,Emilie Le Rhun,Michael Lim,Minesh P. Mehta,Ingo K. Mellinghoff,Giuseppe Minniti,David Nathanson,Michael Platten,Matthias Preusser,Patrick Roth,Marc Sanson,David Schiff,Susan C Short,Martin J B Taphoorn,Joerg C. Tonn,Jonathan Tsang,Roel G.W. Verhaak,Andreas von Deimling,Wolfgang Wick,Gelareh Zadeh,David A. Reardon,Kenneth Aldape,Martin J. van den Bent +39 more
TL;DR: Novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies and viral therapies will be reviewed, as well as the current challenges and future directions for research.
Journal Article
Reversal of Tumoral Immune Resistance by Inhibition of Tryptophan 2,3-Dioxygenase (TDO): Design, Synthesis and Preclinical Evaluation of a Novel TDO Inhibitor.
Eduard Dolusic,Pierre Larrieu,Laurence Moineaux,Vincent Stroobant,Luc Pilotte,Didier Colaux,Benoît Van den Eynde,Bernard Masereel,Johan Wouters,Raphaël Frédérick +9 more
TL;DR: In this paper, the authors showed that enzymatically active Tryptophan 2,3-dioxygenase (TDO) is expressed in a significant proportion of human tumors and developed a TDO inhibitor which, upon systemic treatment, restored the ability of mice to reject TDO-expressing tumors.
References
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Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
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Tissue-based map of the human proteome
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Prevention of allogeneic fetal rejection by tryptophan catabolism
David H. Munn,Min Zhou,John T. Attwood,Igor Bondarev,Simon J. Conway,Brendan Marshall,Corrie C. Brown,Andrew L. Mellor +7 more
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IDO expression by dendritic cells: tolerance and tryptophan catabolism.
Andrew L. Mellor,David H. Munn +1 more
TL;DR: This review summarizes key recent developments and proposes a unifying model for the role of IDO in tolerance induction, including studies of mammalian pregnancy, tumour resistance, chronic infections and autoimmune diseases.
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