Cutaneous T-cell lymphoma: Biologic targets for therapy.
Cutaneous T-cell lymphoma (CTCL) is a malignancy derived from a clonal population of mature, skin-homing lymphocytes. In the skin, the CTCL cells are associated with the Langerhans cells and respond to protumor cytokines. In turn, they upregulate T-cell receptor-dependent signaling pathways and subsequently demonstrate stigmata of T-cell activation. As the disease progresses, there appears to be an accumulation of genetic and epigenetic changes that may contribute to the aggressiveness of the disease. Furthermore, the persistence of tumor appears to require escape from cancer immunosurveillance. This process likely requires modulation of the host immune system and skewing of the immune cells away from a cytotoxic phenotype. Each of these steps in disease pathogenesis offers a potential object for targeted therapies. This article reviews the recent research into the design and use of targeted therapies for CTCL.
Choi
Jaehyuk
J
Medical Oncology, Yale Cancer Center,Yale School of Medicine, New Haven, CT 06520, USA.
Foss
Francine
F
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015704:CD4 Antigens / Q000187:drug effects; D002986:Clinical Trials as Topic; D004167:Diphtheria Toxin / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015195:Drug Design; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D017893:Photopheresis; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019139:Tumor Escape / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015704:CD4 Antigens; D004167:Diphtheria Toxin; D007155:Immunologic Factors; D007376:Interleukin-2; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D007371:Interferon-gamma; C520522:zanolimumab