Anaplastic lymphoma kinase-directed therapy in inflammatory myofibroblastic tumors.
Curr Opin Oncol
; 24(4): 409-13, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22664824
ABSTRACT
PURPOSE OF REVIEW Inflammatory myofibroblastic tumors (IMTs) are indolent mesenchymal neoplasms associated with a small risk of aggressive behavior and metastasis. Surgery is the mainstay of treatment and until recently there have been limited effective treatment options for unresectable disease. This review describes the identification of anaplastic lymphoma kinase (ALK) fusion genes in approximately 50% of IMTs and the role of ALK inhibition in the treatment of this disease. RECENT FINDINGS:
A recent phase I dose-escalation trial of the selective MET/ALK inhibitor crizotinib showed a long-term partial response in a patient with IMT carrying an ALK translocation but not in a patient with ALK-negative disease. Emergence of resistance to crizotinib occurs approximately 5-8 months after initiation of therapy and has been shown to be driven by different mechanisms. Multiple second-generation ALK inhibitors are currently being investigated in the preclinical and clinical trial setting.SUMMARY:
ALK-directed therapy has emerged as a highly effective treatment option for a subset of patients with IMT and pulmonary adenocarcinoma. A number of additional malignancies, including rhabdomyosarcoma, neuroblastoma, anaplastic large cell lymphoma, renal cell carcinoma, and inflammatory breast cancer, have been shown to activate ALK expression by means of ALK fusion proteins, ALK mutations, or increased ALK copy number. Development of more selective ALK inhibitors, which can overcome emergent crizotinib resistance mutations, as well as development of combination treatments with drugs targeting compensatory pathways, will be key to achieving therapeutic success in targeting this potent and prevalent oncogenic driver.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Proteína Tirosina Quinases
/
Granuloma de Células Plasmáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Curr Opin Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos