**3. Combinations Enhancing Tumor Cell Death**

Evasion of cell death is one of the main hallmarks of cancer. Apoptosis resistance develops frequently by either upregulation of anti-apoptotic elements or countering proapoptotic stimuli [149]. Though less prominent, other forms of programmed cell death can be similarly overridden, such as necroptosis [150]. Of note, some viruses employ analogous strategies to counter cell death as an archetypal cellular defense mechanism against viral infection, exemplified by the oncolytic HSV [151] and vaccinia virus [152]. Consequently, viral oncolysis alone rarely leads to widespread and complete cell death, opening the door for a combination approach with cell death sensitizers. Another aspect of such combinations links the aforementioned often limited intra-tumoral spread of OVs with the potential of bystander killing of uninfected cells [153]. Sensitizing a tumor mass with agents promoting cell death has been shown to significantly increase the kill zone of oncolytic viruses beyond the infected areas, yet still confined to the tumor [154]. The following section gives an overview of small molecule compounds that augment tumor cell killing and thus hold promise to synergize with oncolytic virotherapy.
