期刊
LEUKEMIA
卷 28, 期 1, 页码 34-43出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/leu.2013.248
关键词
cancer evolution; clonal heterogeneity; massively parallel sequencing
资金
- American Society of Hematology
- American Cancer Society
- Blavatnik Family Foundation
- Lymphoma Research Foundation
- NHLBI [1RO1HL103532-01, 1RO1HL116452-01]
- NCI [1R01CA155010-01A1]
- Leukemia Lymphoma Translational Research Program Award
- AACR SU2C Innovative Research Grant
The ability of cancer to evolve and adapt is a principal challenge to therapy in general and to the paradigm of targeted therapy in particular. This ability is fueled by the co-existence of multiple, genetically heterogeneous subpopulations within the cancer cell population. Increasing evidence has supported the idea that these subpopulations are selected in a Darwinian fashion, by which the genetic landscape of the tumor is continuously reshaped. Massively parallel sequencing has enabled a recent surge in our ability to study this process, adding to previous efforts using cytogenetic methods and targeted sequencing. Altogether, these studies reveal the complex evolutionary trajectories occurring across individual hematological malignancies. They also suggest that while clonal evolution may contribute to resistance to therapy, treatment may also hasten the evolutionary process. New insights into this process challenge us to understand the impact of treatment on clonal evolution and inspire the development of novel prognostic and therapeutic strategies.
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