Literature DB >> 34201791

Kynurenines as a Novel Target for the Treatment of Malignancies.

Adrian Mor1, Anna Tankiewicz-Kwedlo2, Dariusz Pawlak1.   

Abstract

Malignancies are unquestionably a significant public health problem. Their effective treatment is still a big challenge for modern medicine. Tumors have developed a wide range of mechanisms to evade an immune and therapeutic response. As a result, there is an unmet clinical need for research on solutions aimed at overcoming this problem. An accumulation of tryptophan metabolites belonging to the kynurenine pathway can enhance neoplastic progression because it causes the suppression of immune system response against cancer cells. They are also involved in the development of the mechanisms responsible for the resistance to antitumor therapy. Kynurenine belongs to the most potent immunosuppressive metabolites of this pathway and has a significant impact on the development of malignancies. This fact prompted researchers to assess whether targeting the enzymes responsible for its synthesis could be an effective therapeutic strategy for various cancers. To date, numerous studies, both preclinical and clinical, have been conducted on this topic, especially regarding the inhibition of indoleamine 2,3-dioxygenase activity and their results can be considered noteworthy. This review gathers and systematizes the knowledge about the role of the kynurenine pathway in neoplastic progression and the findings regarding the usefulness of modulating its activity in anticancer therapy.

Entities:  

Keywords:  cancer; cancer treatment; enzyme inhibitors; immune escape; indoleamine 2,3-dioxygenase; kynurenine; kynurenine pathway; tryptophan; tryptophan 2,3-dioxygenase

Year:  2021        PMID: 34201791     DOI: 10.3390/ph14070606

Source DB:  PubMed          Journal:  Pharmaceuticals (Basel)        ISSN: 1424-8247


  184 in total

1.  Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells.

Authors:  Aikou Okamoto; Takashi Nikaido; Kazunori Ochiai; Satoshi Takakura; Misato Saito; Yuko Aoki; Nobuya Ishii; Nozomu Yanaihara; Kyosuke Yamada; Osamu Takikawa; Rie Kawaguchi; Seiji Isonishi; Tadao Tanaka; Mitsuyoshi Urashima
Journal:  Clin Cancer Res       Date:  2005-08-15       Impact factor: 12.531

Review 2.  The kynurenine pathway in brain tumor pathogenesis.

Authors:  Seray Adams; Nady Braidy; Alban Bessede; Alban Bessesde; Bruce J Brew; Ross Grant; Charlie Teo; Gilles J Guillemin
Journal:  Cancer Res       Date:  2012-11-09       Impact factor: 12.701

3.  Expansion of effector memory regulatory T cells represents a novel prognostic factor in lower risk myelodysplastic syndrome.

Authors:  Adam W Mailloux; Chiharu Sugimori; Rami S Komrokji; Lili Yang; Jaroslaw P Maciejewski; Mikkael A Sekeres; Ronald Paquette; Thomas P Loughran; Alan F List; Pearlie K Epling-Burnette
Journal:  J Immunol       Date:  2012-08-08       Impact factor: 5.422

4.  A highly efficient modality to block the degradation of tryptophan for cancer immunotherapy: locked nucleic acid-modified antisense oligonucleotides to inhibit human indoleamine 2,3-dioxygenase 1/tryptophan 2,3-dioxygenase expression.

Authors:  Richard Klar; Sven Michel; Monika Schell; Lisa Hinterwimmer; Alfred Zippelius; Frank Jaschinski
Journal:  Cancer Immunol Immunother       Date:  2019-12-04       Impact factor: 6.968

5.  Indoleamine 2,3-dioxygenase promotes peritoneal dissemination of ovarian cancer through inhibition of natural killercell function and angiogenesis promotion.

Authors:  Hiroaki Nonaka; Yasushi Saga; Hiroyuki Fujiwara; Hidetoshi Akimoto; Akiyo Yamada; Syota Kagawa; Yuji Takei; Shizuo Machida; Osamu Takikawa; Mitsuaki Suzuki
Journal:  Int J Oncol       Date:  2011-01       Impact factor: 5.650

6.  Increased levels of 3-hydroxykynurenine in different brain regions of rats with chronic renal insufficiency.

Authors:  Joanna Topczewska-Bruns; Dariusz Pawlak; Ewa Chabielska; Anna Tankiewicz; Wlodzimierz Buczko
Journal:  Brain Res Bull       Date:  2002-08-15       Impact factor: 4.077

Review 7.  IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance.

Authors:  David H Munn; Andrew L Mellor
Journal:  Trends Immunol       Date:  2016-01-31       Impact factor: 16.687

8.  Induction and role of indoleamine 2,3 dioxygenase in mouse models of influenza a virus infection.

Authors:  Lei Huang; Lingqian Li; Kim D Klonowski; S Mark Tompkins; Ralph A Tripp; Andrew L Mellor
Journal:  PLoS One       Date:  2013-06-13       Impact factor: 3.240

9.  The extracts of Astragalus membranaceus enhance chemosensitivity and reduce tumor indoleamine 2, 3-dioxygenase expression.

Authors:  Naphichaya Phacharapiyangkul; Li-Hsien Wu; Wei-Ya Lee; Yi-Hsuan Kuo; Yueh-Jung Wu; Huei-Pu Liou; Yung-En Tsai; Che-Hsin Lee
Journal:  Int J Med Sci       Date:  2019-08-06       Impact factor: 3.738

10.  Differential kynurenine pathway metabolism in highly metastatic aggressive breast cancer subtypes: beyond IDO1-induced immunosuppression.

Authors:  Benjamin Heng; Ayse A Bilgin; David B Lovejoy; Vanessa X Tan; Heloisa H Milioli; Laurence Gluch; Sonia Bustamante; Tharani Sabaretnam; Pablo Moscato; Chai K Lim; Gilles J Guillemin
Journal:  Breast Cancer Res       Date:  2020-10-27       Impact factor: 6.466

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  5 in total

Review 1.  Indoleamine 2,3-Dioxygenase 1: A Promising Therapeutic Target in Malignant Tumor.

Authors:  Xiaotian Song; Qianqian Si; Rui Qi; Weidan Liu; Miao Li; Mengyue Guo; Lin Wei; Zhiyan Yao
Journal:  Front Immunol       Date:  2021-12-23       Impact factor: 7.561

Review 2.  Tryptophan-Kynurenine Pathway in COVID-19-Dependent Musculoskeletal Pathology: A Minireview.

Authors:  Sagar Vyavahare; Sandeep Kumar; Nicholas Cantu; Ravindra Kolhe; Wendy B Bollag; Meghan E McGee-Lawrence; William D Hill; Mark W Hamrick; Carlos M Isales; Sadanand Fulzele
Journal:  Mediators Inflamm       Date:  2021-10-05       Impact factor: 4.711

Review 3.  Metabolic Changes in Tumor Microenvironment: How Could They Affect γδ T Cells Functions?

Authors:  Anna Maria Corsale; Marta Di Simone; Elena Lo Presti; Carmela Picone; Francesco Dieli; Serena Meraviglia
Journal:  Cells       Date:  2021-10-26       Impact factor: 6.600

Review 4.  Molecular Targets of Natural Compounds with Anti-Cancer Properties.

Authors:  Małgorzata Kubczak; Aleksandra Szustka; Małgorzata Rogalińska
Journal:  Int J Mol Sci       Date:  2021-12-20       Impact factor: 5.923

5.  Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties.

Authors:  Elżbieta Studzińska-Sroka; Aleksandra Majchrzak-Celińska; Przemysław Zalewski; Dominik Szwajgier; Ewa Baranowska-Wójcik; Barbara Kaproń; Tomasz Plech; Marcin Żarowski; Judyta Cielecka-Piontek
Journal:  Pharmaceuticals (Basel)       Date:  2021-12-10
  5 in total

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