Concise review: cancer cells escape from oncogene addiction: understanding the mechanisms behind treatment failure for more effective targeting.
Oncogene addiction describes the dependence of some cancers on one or a few genes for their survival. Inhibition of the corresponding oncoproteins can lead to dramatic responses. However, in some cases, such as chronic myeloid leukemia (CML), a disease characterized by the presence of the abnormal fusion tyrosine kinase BCR-ABL, cancer stem cells may never acquire addiction to the oncogene that drives disease development. The suggested mechanism(s) for treatment failure include a quiescent stem cell population capable of reinstating disease, high levels of oncoprotein expression, or acquired mutations in the oncogene. In this review, we discuss the evidence for oncogene addiction in several solid tumors and their potential escape mechanism(s) with a particular focus on CML stem cells.
['Pellicano|Francesca|F|', 'Mukherjee|Leena|L|', 'Holyoake|Tessa L|TL|']
D006801:Humans D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive D058990:Molecular Targeted Therapy D009369:Neoplasms D014411:Neoplastic Stem Cells D009857:Oncogenes D017211:Treatment Failure
Cancer cells Oncogene addiction Chronic myeloid leukemia BCR-ABL Adult stem cells Hemopoietic stem cells Tyrosine kinase inhibitors