1. Supplementary Table 1 A. B. CI simulations display synergism (CI 1) for the entire spectrum of effect levels (Fa) in the combination of NFV and BZ (right panel). CIs for experimental values (left panel) are displayed as actual Fa-CI plots in Figure 1B. CIs for experimental values are displayed as actual Fa-CI plots in Figure 1D.

2. Percent sub-G1 DNA Percent cell death DMSONFVBortezomibNFV+BortezomibDMSONFVBortezomibNFV+Bortezomib DMSO NFV Bortezomib Z-VAD PARP Cleaved PARP + - - - ++ + ++++ ++- - ------ -- -- +-+-+-+ - Z-VAD + Z-VAD - Z-VAD + Z-VAD * * RPMI8226 Supplementary Figure 1

3. H157 DR5 precursor DR4 DR5 mature α-Tubulin Bcl-2 Bax Fas NFV DMSO Bortezomib - 0.5 h8 h24 h -++--++--++ -+-+-+-+-+-+ +---+---+--- Mcl-1 Actin Supplementary Figure 2

4. P-Akt (S473) Total Akt P-Akt (T308) P-p44/42 α-Tubulin P-JNK (54/46 kDa) P-p38 Total p44/42 Total p38 NFV DMSO Bortezomib - 0.5 h8 h24 h -++--++--++ -+-+-+-+-+-+ +---+---+--- H157 Supplementary Figure 3

5. P-eIF2α ATF3 2435 Vehicle NFV GAPDH 1 Bortezomib CHOP C1 PARP C2 Bip Total-eIF2α XBP-1 s Cleaved PARP Caspase 3 Cleaved Caspase 3 243512435124351 NFV+Bortezomib H157 Xenograft tumor lysates Supplementary Figure 4 A.

6. HSP70 Ubiqutin 2435 Vehicle NFV GAPDH 1 Bortezomib NFV+Bortezomib C1C2 243512435124351 H157 Xenograft tumor lysates B.

7. RPMI8226 Xenograft tumor lysates C. ATF3 VNBzN+Bz Expression ratio to vehicle CHOP Expression ratio to vehicle VNBzN+Bz

8. Supplementary Figure 5

9. Supplementary Figure 6