CYCS and glioblastoma: Activation of anti-apoptotic proteins can reduce tumor sensitivity to chemotherapy.709 Bcl-2 is the major anti-apoptotic protein that inhibits tumor cell apoptosis by inhibiting the release of apoptosis-inducing factors and cytochrome c from mitochondria.710,711 Shuai et al. loaded siRNA and DOX through PEI-based PNPs with folic acid modification for GBM combination therapy.712 As mentioned previously, the high expression of miR-21 contributes to drug resistance and the proliferation of GBM.