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Other metabolic targets
[108]
Other studies have been focused on TCA intermediates. Sanchez et al. were able to identify dichloroacetate
(DCA) as a possible target for cancer therapy. DCA is an activator for pyruvate dehydrogenase which allows
for increased production of TCA intermediates and consequently, increased OXPHOS for ATP production.
Subsequently, DCA was found to inhibit glycolysis in multiple myeloma and increase sensitivity to bortezomib.

CONCLUSION
The study of metabolism’s role in MM remains in its infancy, and many avenues remain unexplored. With
combination therapies being the norm in myeloma management and acquired resistance to conventional
therapies remaining a challenge, the potential exists for additional adjunctive therapies in MM patients.
Targeting metabolic pathways is a novel area with preclinical data suggesting efficacy. Targets such as the
GLUT and MCT transporters, IGF-1, FAS, and metabolites of the ETC and OXPHOS warrant additional
exploration as possible novel anti-myeloma strategies, but care must be taken to minimize adverse effects
when targeting ubiquitous pathways. Ideally, future preclinical and clinical studies will help to elucidate
metabolism’s role in myeloma development and progression, and may lead to the discovery of novel therapies
for patients suffering from this disorder.

DECLARATIONS
Authors’ contributions
All authors wrote the manuscript.

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by NHLBI (K08HL103780), NCI (R01CA197792, R44CA199767, R21CA234701);
NIH (5T32HL007057-42); and a pilot grant from the Opportunity Funds Management Core of the Centers
for Medical Countermeasures against Radiation, National Institute of Allergy and Infectious Diseases
(U19AI067773).

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

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