Viral Elements Sense Tumorigenic Processes:Approaching Selective Cancer Therapy

Klaas      Kooistra; Ying-Hui      Zhang; Mathieu   H.M.   Noteborn

Abstract

Viruses can produce viral oncoproteins that drive multiple genetic alterations as the consequence of neoplastic transformation. Viral proteins encoded by onco-related viruses such as polyomavirus SV40 or Epstein-Barr virus are involved in cellular processes resulting in imbalance between proliferation and cell death, knowledge of which continues to be crucial for combating cancer. On the other hand, viruses also generate viral components that, from a cold viral protein, can become a tumor-selective killer by sensing cellular tumorigenic hallmarks. For instance, the avian virus derived apoptin protein has been proven to induce tumor-regression in various pre-clinical animal models without showing detectable side effects. In particular, apoptin-interacting protein partners such as components of the anaphase promoting complex were identified as potential anticancer drug targets. The adenovirus-derived protein E4orf4, another viral protein with tumor-specific apoptosis characteristics, has been proven to interact with the tumor-suppressor protein phosphatase 2A. This review aims to describe recent studies with representative viral elements that have contributed to our understanding of critical tumorigenic processes and have conferred an impact on the development of novel anti-cancer therapies.

Keywords: Anti-cancer therapies, apoptin, apoptosis, drug targets, E4orf4, Simian virus 40 (SV40), large tumor antigen (LT) and small tumor antigen (st), tumorigenesis