BCL2 and cancer: Although the molecular mechanisms underlying the decreased susceptibility of cancer cells to TRAIL-driven apoptosis have not been completely unraveled, the downregulation of DR4 and DR5, upregulation of DcR1 and DcR2 [11,20], and overexpression of c-FLIP and anti-apoptotic proteins belonging to both the Bcl-2 (for example, Bcl-2, Bcl-xL, MCL-1) and cellular inhibitor of apoptosis protein (IAP)—for example, X-linked inhibitor of apoptosis protein (XIAP), survivin—families are the most frequently proposed TRAIL resistance factors [11,20].