期刊
CURRENT OPINION IN HEMATOLOGY
卷 20, 期 4, 页码 374-381出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0b013e3283623c07
关键词
anaplastic lymphoma kinase; kinase inhibitors; lymphoid differentiation; mouse models; signalling pathways
类别
资金
- Italian Association for Cancer Research (AIRC) Special Program in Clinical Molecular Oncology, Milan [10007]
- Regione Piemonte (ONCOPROT) [CIPE 25/2005]
- ImmOnc (Innovative approaches to boost the immune responses, Programma Operativo Regionale, Piattaforme Innovative) [BIO F.E.S.R. 2007/13, LR 34/2004]
- Oncology Program of Compagnia di San Paolo, Torino
- Partnership for Cure, NIH [1 P50 MH094267-01, NIH 1 U54 CA121852-05, NIH 1R01CA164152-01]
- Oncosuisse (Bern, Switzerland) [KLS-02403-02-2009]
- Anna Lisa Stiftung (Ascona, Switzerland)
- Nelia and Amadeo Barletta Foundation (Lausanne, Switzerland)
Purpose of reviewAnaplastic large cell lymphomas (ALCLs) are rare entities whose somatic genetic lesions have been identified only in a subset of patients. Thus, an integrated and massive discovery programme is required to define their tumourigenic alterations and to design more successful tailored therapies.Recent findingsThe discovery of anaplastic lymphoma kinase (ALK) fusions has provided the basis for the characterization of distinct subsets among ALCL patients. Although the oncogenic addiction of ALK signalling is proven, the tumorigenic contribution of coactivating lesions is still missing. As ALK- and ALK+ share common signatures, it is plausible that analogous mechanisms of transformation may be operating in both subsets, as confirmed by the dysregulated activation of c-MYC, RAS and NFB, and the loss of Blimp-1 and p53/p63 axis. Nonetheless, recurrent genetic alterations for ALK- ALCL or refractory leukaemic ALK+ ALCL are lacking. Moreover, although conventional chemotherapies (anthracycline-based) are most successful, that is in ALK+ ALCL patients, the implementation of ALK inhibitors or of anti-CD30 based treatments provides innovative solutions, particularly in paediatric ALK+ ALCL and in chemorefractory/relapsed patients.SummaryThe complete portrayal of the landscape of genetic alterations in ALCL will dictate the development of innovative chemotherapeutic and targeted therapies that will fit most with the molecular and clinical profiling of individual patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据