Next Article in Journal
Sirtuins in Alzheimer’s Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics
Previous Article in Journal
Efficient Editing of the Nuclear APT Reporter Gene in Chlamydomonas reinhardtii via Expression of a CRISPR-Cas9 Module
Previous Article in Special Issue
TRAF6 Silencing Attenuates Multiple Myeloma Cell Adhesion to Bone Marrow Stromal Cells
Open AccessReview

The Impact of Tumor Heterogeneity on Diagnostics and Novel Therapeutic Strategies in Multiple Myeloma

1
Department of Internal Medicine 2, University Hospital of Würzburg, 97080 Würzburg, Germany
2
Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
3
Department of Internal Medicine V, University Hospital of Heidelberg, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1248; https://doi.org/10.3390/ijms20051248
Received: 15 February 2019 / Revised: 8 March 2019 / Accepted: 9 March 2019 / Published: 12 March 2019
(This article belongs to the Special Issue Novel Therapeutic Strategies in Multiple Myeloma)
Myeloma is characterized by extensive inter-patient genomic heterogeneity due to multiple different initiating events. A recent multi-region sequencing study demonstrated spatial differences, with progression events, such as TP53 mutations, frequently being restricted to focal lesions. In this review article, we describe the clinical impact of these two types of tumor heterogeneity. Target mutations are often dominant at one site but absent at other sites, which poses a significant challenge to personalized therapy in myeloma. The same holds true for high-risk subclones, which can be locally restricted, and as such not detectable at the iliac crest, which is the usual sampling site. Imaging can improve current risk classifiers and monitoring of residual disease, but does not allow for deciphering the molecular characteristics of tumor clones. In the era of novel immunotherapies, the clinical impact of heterogeneity certainly needs to be re-defined. Yet, preliminary observations indicate an ongoing impact of spatial heterogeneity on the efficacy of monoclonal antibodies. In conclusion, we recommend combining molecular tests with imaging to improve risk prediction and monitoring of residual disease. Overcoming intra-tumor heterogeneity is the prerequisite for curing myeloma. Novel immunotherapies are promising but research addressing their impact on the spatial clonal architecture is highly warranted. View Full-Text
Keywords: multiple myeloma; spatial heterogeneity; risk stratification; minimal residual disease; targeted therapy; clinical imaging; immunotherapy; daratumumab multiple myeloma; spatial heterogeneity; risk stratification; minimal residual disease; targeted therapy; clinical imaging; immunotherapy; daratumumab
Show Figures

Figure 1

MDPI and ACS Style

Rasche, L.; Kortüm, K.M.; Raab, M.S.; Weinhold, N. The Impact of Tumor Heterogeneity on Diagnostics and Novel Therapeutic Strategies in Multiple Myeloma. Int. J. Mol. Sci. 2019, 20, 1248.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop