Exome sequencing in tracking clonal evolution in multiple myeloma following therapy.

Tumour Immunogenetics Group, Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 9.38). 10/2012; DOI: 10.1038/leu.2012.287
Source: PubMed
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.Leukemia accepted article preview online, 27 August 2013. doi:10.1038/leu.2013.248.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2013; 28(1). DOI:10.1038/leu.2013.248 · 9.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In spite of significant advances in the management of multiple myeloma (MM), the disease remains incurable and nearly all patients ultimately relapse and require salvage chemotherapy. As such, relapsed and relapsed-refractory MM remains a critical area of research pertaining to biological mechanisms of progression and chemotherapy resistance, as well as to the development of new pharmacologic agents and immunologic approaches for the disease. The immunomodulatory agents and proteasome inhibitors represent the cornerstone of treatment in this setting, with combination regimens incorporating these drugs demonstrating encouraging rates and duration of response, including the newer agents, pomalidomide and carfilzomib. In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.
    Expert Review of Hematology 01/2014; DOI:10.1586/17474086.2014.882764 · 2.14 Impact Factor
  • Source
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2014; 28(7). DOI:10.1038/leu.2014.59 · 9.38 Impact Factor