CASP8 and neoplasm: These drugs affect both (1) the primary tumor growth by binding to DNA, inducing double strand breaks, preventing DNA repair, and inhibiting the active transcription through structural changes of DNA and degradation of RNA polymerase II through the ubiquitin-proteasome pathway [58], and (2) the TME via modulation of the cytokine expression in the cancer cells through regulation of their transcription and depletion of TAMs by inducing overexpression of TRAIL receptors, their recruitment in lipid rafts, ligand-independent activation, and subsequent caspase-8-mediated apoptosis.