Simultaneous targeting of mitochondrial metabolism and immune checkpoints as a new strategy for renal cancer therapy.

(D) Orthotopic tumours were generated by surgical grafting of RenCa cells in left kidney of Balb-c mice (5 × 104 cells per animal), and the animals treated i.p. with MitoTam at 4 mg/kg twice per week for 2 weeks. PD-1 showed an additive affect with MitoTam in RenCa cell tumours (Figure 4H and I) similar to that for the combination of MitoTam with PD-L1 presented above. Using human and a mouse renal cancer cell lines, we found that MitoTam killed the cells with IC SB 50 sb of 0.3-1.4 M (Figure 1C, Figure S1E) even after its removal from cell culture media (Figure 1D). Cancer is a pathology still on the rise,1 with unmet need for efficient therapy, owing to factors such as considerable differences in mutational signature in the same patient in primary tumours and proximal/distal metastases, shown, for example, for renal cancer.2 What is needed then is an invariant target predominantly only affected by drugs in cancer cells. [Extracted from the article]