Viral therapy for cancer and cancer stem cells

One of the upcoming approaches for the treatment of cancer is the use of the scourge of mankind - the virus. This mode of therapy takes advantage of firstly, the tumor's ability to downregulate immune response and secondly, the virus' ability to specifically target a cell for infection. These genetically-engineered viruses have their pathogenic ability attenuated, but are designed to infect, replicate and lyse tumor cells, and subsequently spread to other tumor cells (Kooby et al, 1999, Suzuki and Curiel, 2001) when the immune response is downregualted by the tumor. Thus, viral therapy offers an interesting alternative to chemotherapy.

However, the issue with cancer treatment by any form of therapy is the problem posed by cancer stem cells, which can metastasize to distant sites and give rise to a heterogeneous population of cells (Kucia et al, 2005). Cancer stem cells have been found in brain cancer, breast cancer and colorectal cancer. As with any other therapy, targeting these cancer stem cells is paramount. With regards to viral infection of stem cells, I have found this intersting paper by Kosugi et al, whereby the investigators used cytomegalovirus to infect stem cells of the central nervous system. Interestingly, the virus-infected stem cells exhibited inhibited growth and DNA replication. As an afterthought, I was wondering if a cytomegalovirus, with its ability to infect stem cells, can be used in the fight against cancer stem cells of the brain cancer. Obviously, some genetic engineering has to be done. The cytomegalovirus is also capable of a lytic phase that can lyse and subsequently infect the other cancer cells (Anders and Punturieri, 1991).

Citations

1) Kooby DA, Carew JF, Halterman MW, Mack JE, Bertino JR, Blumgart LH, Federoff HJ, Fong Y. Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207). FASEB J. 1999 Aug;13(11):1325-34.

2) Suzuki K, Curiel DT. Viral therapy of cancer. Rev Invest Clin. 2001 Jul-Aug;53(4):346-56.

3) Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells. 2005 Aug;23(7):879-94.

4) Kosugi I, Shinmura Y, Kawasaki H, Arai Y, Li RY, Baba S, Tsutsui Y. Cytomegalovirus infection of the central nervous system stem cells from mouse embryo: a model for developmental brain disorders induced by cytomegalovirus. Lab Invest. 2000 Sep;80(9):1373-83.

5) Anders DG, Punturieri SM. Multicomponent origin of cytomegalovirus lytic-phase DNA replication. J Virol. 1991 Feb;65(2):931-7.