Although further study is needed to confirm whether specific inhibition of the 20S proteasome assembled by the NRF3-POMP axis reduces cancer development, our findings shed light on the potential to reposition anti-HIV agents, such as HIVp inhibitors, as anticancer drugs in order to inhibit DDI2 and indirectly inhibit the tumorigenic function of NRF3. The gene discussed is NFE2L3; the disease is cancer.