title: Novel therapeutic options in anaplastic large cell lymphoma: molecular targets and immunological tools.
abstract: Anaplastic large cell lymphoma (ALCL) is a CD30-positive, aggressive T-cell lymphoma, and about half of the patients with this disease harbor the t(2;5)(p21;q35) translocation. This chromosomal aberration leads to fusion of the NPM gene with the ALK tyrosine kinase, leading to its constitutive activation. To date, treatment options include polychemotherapy (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone), which is sometimes combined with radiation in the case of bulky disease, leading to remission rates of ∼80%. However, the remaining patients do not respond to therapy, and some patients experience chemo-resistant relapses, making the identification of new and better treatments imperative. The recent discovery of deregulated ALK in common cancers such as non-small cell lung cancer and neuroblastoma has reinvigorated industry interest in the development of ALK inhibitors. Moreover, it has been shown that the ALK protein is an ideal antigen for vaccination strategies due to its low expression in normal tissue. The characterization of microRNAs that are deregulated in ALCL will yield new insights into the biology of ALCL and open new avenues for therapeutic approaches in the future. Also, CD30 antibodies that have been tested in ALCL for quite a while will probably find a place in forthcoming treatment strategies.
authors.affiliation: Laboratory for Immunological and Molecular Cancer Research, Third Medical Department, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, 5020 Salzburg, Austria. o.merkel@salk.at
authors.forename: Olaf
authors.initials: O
authors.lastname: Merkel
authors.forename: Frank
authors.initials: F
authors.lastname: Hamacher
authors.forename: Eveline
authors.initials: E
authors.lastname: Sifft
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000276:immunology* / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen; D047428:Protein Kinase Inhibitors; C107023:p80(NPM-ALK) protein; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases