Anaplastic lymphoma kinase and its signalling molecules as novel targets in lymphoma therapy.
A crucial issue in the development of molecularly-targeted anticancer therapies is the identification of appropriate molecules whose targeting would result in tumour regression with a minimal level of systemic toxicity. Anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase, normally expressed at low levels in the nervous system. As a consequence of chromosomal translocations involving the alk gene (2p23), ALK is also aberrantly expressed and constitutively activated in approximately 60% of CD30+ anaplastic large cell lymphomas (ALCLs). Due to the selective overexpression of ALK in tumour cells, its direct involvement in the process of malignant transformation and its frequent expression in ALCL patients, the authors recognise ALK as a suitable candidate for the development of molecularly targeted strategies for the therapeutic treatment of ALK-positive lymphomas. Strategies targeting ALK directly or indirectly via the inhibition of the protein networks responsible for ALK oncogenic signalling are discussed.
Coluccia
A M L
AM
Oncogenic Fusion Genes and Proteins Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Gunby
R H
RH
Tartari
C J
CJ
Scapozza
L
L
Gambacorti-Passerini
C
C
Passoni
Lorena
L
D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases