Therapeutic challenges in peripheral T-cell lymphoma

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Abstract

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral T-Cell Lymphomas (r/r PTCL), resulting in highly unsatisfactory treatment outcomes for these patients. This review provides an overview of potential mechanisms contributing to PTCL treatment resistance, encompassing aspects such as tumor heterogeneity, tumor microenvironment, and abnormal signaling pathways in PTCL development. The existing drugs aimed at overcoming PTCL resistance and their potential resistance mechanisms are also discussed. Furthermore, a summary of ongoing clinical trials related to PTCL is presented, with the aim of aiding clinicians in making informed treatment decisions.

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Most cited references 138

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The 2016 revision of the World Health Organization classification of lymphoid neoplasms.

Steven H. Swerdlow, Elias Campo, Stefano Pileri … (2016)

A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms.

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A view on drug resistance in cancer

Neil Vasan, José Baselga, David Hyman (2019)

The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy.

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Control of regulatory T cell development by the transcription factor Foxp3.

Shohei Hori, Takashi Nomura, Shimon Sakaguchi (2003)

Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.

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Author and article information

Contributors

Yunpeng Luan: luanyunpeng@ynutcm.edu.cn

Dong-Hua Yang: dong-hua.yang@nyctcm.edu

Journal

Journal ID (nlm-ta): Mol Cancer

Journal ID (iso-abbrev): Mol Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date (Electronic): 4 January 2024

Publication date PMC-release: 4 January 2024

Publication date Collection: 2024

Volume: 23

Electronic Location Identifier: 2

Affiliations

[1 ]The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, ( https://ror.org/04zap7912) Kunming, 650021 China

[2 ]GRID grid.412720.2, ISNI 0000 0004 1761 2943, Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, , Southwest Forestry University, ; Kunming, 650224 China

[3 ]GRID grid.419409.1, ISNI 0000 0001 0109 1950, NMPA Key Laboratory for Safety Research and Evaluation of Innovative Drugs, Beijing Key Laboratory of Analysis and Evaluation On Chinese Medicine, , Beijing Institute for Drug Control, ; Beijing, 102206 China

[4 ]The Affiliated Hospital of Kunming University of Science and Technology, ( https://ror.org/00xyeez13) Kunming, 650032 China

[5 ]New York College of Traditional Chinese Medicine, ( https://ror.org/03ccevd14) 200 Old Country Rd, Suite 500, Mineola, NY 11501 USA

Article

Publisher ID: 1904

DOI: 10.1186/s12943-023-01904-w

PMC ID: 10765866

PubMed ID: 38178117

SO-VID: 1de58316-12ed-48e1-9e26-b4a28aa790c8

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 24 July 2023

Date accepted : 16 November 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 32160223

Award ID: 31860254

Award ID: 32160223

Award Recipient : Yunpeng Luan Qinzuo Dong Shili Ye Jun Yang

Funded by: General Program of Science and Technology Department of Yunnan Provincial

Award ID: 2018FG001-039

Award Recipient : Xiang Li Yunqi Luan Junyu Luo

Funded by: Reserve Talents Project for Young and Middle-aged Academic and Technical Leaders of the Department of Science and Technology of Yunnan Province

Award ID: 202105AC160047

Award Recipient : Qinzuo Dong Shili Ye

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: leukemia,lymphoma,ptcl,nhl,t-all,alcl,tme,relapse,refractory,drug resistance,clinical trial

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: leukemia, lymphoma, ptcl, nhl, t-all, alcl, tme, relapse, refractory, drug resistance, clinical trial

Therapeutic challenges in peripheral T-cell lymphoma

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Abstract

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Karger: Oncology

Most cited references 138

The 2016 revision of the World Health Organization classification of lymphoid neoplasms.

A view on drug resistance in cancer

Control of regulatory T cell development by the transcription factor Foxp3.

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