Novel targeted therapies of T cell lymphomas. 2020

Katarzyna Iżykowska, and Karolina Rassek, and Dorota Korsak, and Grzegorz K Przybylski
Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland.

T cell lymphomas (TCL) comprise a heterogeneous group of non-Hodgkin lymphomas (NHL) that often present at an advanced stage at the time of diagnosis and that most commonly have an aggressive clinical course. Treatment in the front-line setting is most often cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens, which are effective in B cell lymphomas, but in TCL are associated with a high failure rate and frequent relapses. Furthermore, in contrast to B cell NHL, in which substantial clinical progress has been made with the introduction of monoclonal antibodies, no comparable advances have been seen in TCL. To change this situation and improve the prognosis in TCL, new gene-targeted therapies must be developed. This is now possible due to enormous progress that has been made in the last years in the understanding of the biology and molecular pathogenesis of TCL, which enables the implementation of the research findings in clinical practice. In this review, we present new therapies and current clinical and preclinical trials on targeted treatments for TCL using histone deacetylase inhibitors (HDACi), antibodies, chimeric antigen receptor T cells (CARTs), phosphatidylinositol 3-kinase inhibitors (PI3Ki), anaplastic lymphoma kinase inhibitors (ALKi), and antibiotics, used alone or in combinations. The recent clinical success of ALKi and conjugated anti-CD30 antibody (brentuximab-vedotin) suggests that novel therapies for TCL can significantly improve outcomes when properly targeted.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074322 Antineoplastic Agents, Immunological Antineoplastic agents containing immunological agents (e.g. MAbs). These pharmacologic preparations inhibit or prevent the proliferation of NEOPLASMS. Antineoplastic MAbs,Antineoplastics, Monoclonal Antibodies,Antineoplastics, Monoclonal Antibody,MAbs, Antineoplastic,Monoclonal Antibodies, Antineoplastic,Antibodies Antineoplastics, Monoclonal,Antineoplastic Monoclonal Antibodies,Immunological Antineoplastic Agents,Monoclonal Antibodies Antineoplastics,Monoclonal Antibody Antineoplastics
D000077548 Anaplastic Lymphoma Kinase A receptor tyrosine kinase that is essential for development and differentiation of the nervous system in response to secreted growth factors. It phosphorylates the first tyrosine of the Y-x-x-x-Y-Y motif of targets that include PROTO-ONCOGENE PROTEINS C-CBL; INSULIN RECEPTOR SUBSTRATE-1; and MITOGEN-ACTIVATED PROTEIN KINASES, leading to activation of the MAPK signaling pathway and cell proliferation. A chromosomal aberration involving the ALK gene results in its constitutive expression in some cases of NON-HODGKIN LYMPHOMA. ALK Kinase,ALK Tyrosine Kinase Receptor,Anaplastic Lymphoma Receptor Tyrosine Kinase,CD246 Antigen,NPM-ALK,Nucleophosmin-Anaplastic Lymphoma Kinase,Nucleophosmin Anaplastic Lymphoma Kinase
D000081082 Phosphoinositide-3 Kinase Inhibitors Agents that inhibit PHOSPHOINOSITIDE-3 KINASE activity. Phosphoinositide-3 Kinase Inhibitor,Inhibitor, Phosphoinositide-3 Kinase,Inhibitors, Phosphoinositide-3 Kinase,Kinase Inhibitor, Phosphoinositide-3,Kinase Inhibitors, Phosphoinositide-3,Phosphoinositide 3 Kinase Inhibitor,Phosphoinositide 3 Kinase Inhibitors
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016219 Immunotherapy, Adoptive Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314) Adoptive Cellular Immunotherapy,Adoptive Immunotherapy,CAR T-Cell Therapy,Cellular Immunotherapy, Adoptive,Chimeric Antigen Receptor Therapy,Immunotherapy, Adoptive Cellular,Adoptive Cellular Immunotherapies,Adoptive Immunotherapies,CAR T Cell Therapy,CAR T-Cell Therapies,Cellular Immunotherapies, Adoptive,Immunotherapies, Adoptive,Immunotherapies, Adoptive Cellular,T-Cell Therapies, CAR,T-Cell Therapy, CAR,Therapies, CAR T-Cell,Therapy, CAR T-Cell
D016399 Lymphoma, T-Cell A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes. T-Cell Lymphoma,Lymphoma, T Cell,Lymphomas, T-Cell,T Cell Lymphoma,T-Cell Lymphomas
D056572 Histone Deacetylase Inhibitors Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains. HDAC Inhibitor,HDAC Inhibitors,Histone Deacetylase Inhibitor,Deacetylase Inhibitor, Histone,Deacetylase Inhibitors, Histone,Inhibitor, HDAC,Inhibitor, Histone Deacetylase,Inhibitors, HDAC,Inhibitors, Histone Deacetylase
D058990 Molecular Targeted Therapy Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease. Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular
D018796 Immunoconjugates Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers. Antibody Drug Conjugate,Antibody-Drug Conjugate,Radioimmunoconjugates,Antibody-Drug Conjugates,Immunoconjugate,Radioimmunoconjugate,Antibody Drug Conjugates,Conjugate, Antibody Drug,Conjugate, Antibody-Drug,Conjugates, Antibody-Drug,Drug Conjugate, Antibody

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