Yazarlar : Helgason GV, Karvela M, Holyoake TL.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/21693757

Konu : Lösemi

Literatür İçeriği :

Abstract

The introduction of imatinib in the treatment of chronic myeloid leukaemia (CML) represents the most successful example of targeted therapy in human cancer. However, leukaemic stem cells (LSCs) are insensitive to tyrosine kinase inhibitors (TKIs) and contribute to disease persistence by representing a reservoir of self-renewing cells that replenish the disease upon drug discontinuation. This has re-focused the interest of scientists towards drug combinations i.e. treating with TKIs and simultaneously targeting alternative survival mechanisms. One candidate target mechanism is autophagy, a cellular recycling process that acts as a cytoprotective shield in CML cells in response to TKI-induced stress and in other cancer cells surviving in an inhospitable microenvironment. On that basis, inhibition of autophagy has now become an exciting option for combination treatment in cancer and clinical trials have been initiated in solid and haemopoietic tumours such as CML, chronic lymphocytic leukaemia (CLL) and multiple myeloma. This review describes the biology of CML and elucidates how the molecular driver BCR-ABL led to the development of TKIs. We then discuss the molecular regulation of autophagy and the potential for autophagy inhibition as the next step in our attempt to tackle the problem of CML persistence to offer a curative option.

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