Melanoma addiction to GCDH defines NRF2 tumor suppressor function
Prof. Ze’ev Ronai Director, NCI designated Cancer Center
Sanford-Burnham-Prebys
Medical Discovery Institute
18 November 2021
Tumor dependency on specific metabolic signals has guided numerous therapeutic
approaches. Here we identify melanoma addiction to the lysine metabolism pathway,
which defines NRF2 tumor suppressor function. Inhibition of select lysine catabolism
components, either genetically, or by newly identified small molecules, effectively
attenuates NRF2 tumor suppressor function and induces melanoma cell death, seen in
culture as in inhibition of melanoma in mice. Addiction to lysine catabolism is independent
of genetic driver mutations. Addiction to lysine catabolism pathway components, which
define NRF2 tumor suppressor function, offers a new paradigm for the control of NRF2
oncogenic vs. tumor suppressor activities, while highlighting a novel therapeutic modality
for treatment of melanoma.
