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Page 362 Raczka et al. Cancer Drug Resist 2019;2:356-64 I http://dx.doi.org/10.20517/cdr.2018.004

achieving long-term stable disease. This suggests that it may be most effective in combination with other
agents. In April 2018, the FDA granted Fast Track designation for CB-839 plus Cabo based on encouraging
activity from a Phase 1 trial in heavily pre-treated mRCC patients. Combination therapy of CB-839 with
everolimus requires more data to assess its efficacy. Since there is such a significant burden of resistance to
currently available treatments, resistance may also be an issue for new treatments. Indeed, metabolomic
studies of an allosteric and reversible inhibitor of GLS, C.968, found that lipid catabolism is activated to
[59]
compensate for inhibition of glutaminolysis in several cancer cells . This suggests that further genetic
and metabolomic studies will be crucial for the successful implementation of CB-839 into routine clinical
practice.

DECLARATIONS
Authors’ contributions
Wrote, read and approved the final manuscript: Both authors

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by the Melville Trust for Care and Cure of Cancer.

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

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Authors 2019.

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