Table 2A. RNA, double-strand virus design, mechanisms of action and clinical implications.
| Virus | Design | Clinical Implications |
|---|---|---|
| Reovirus | · RAS-induced inhibition of cellular PKR is responsible for preferential activity in RAS-activated cells, allowing viral translation, replication, oncolysis and cancer cell death [8]. · RAS activated JNK and NFkB can mediate reovirus- induced apoptosis [218, 219]. · Reovirus can induce antitumor immune responses [14]. · Reovirus can preferentially infect and kill pancreatic cancer cells [116, 117] |
· Preclinical data: wild-type reovirus type 3 Dearing (Reolysin), has demonstrated synergy and/or additive effects with standard chemotherapies [107, 111–114]. · Preclinical data: the combination with immune-modulating chemotherapeutic drugs may enhance the antitumor effects by attenuating the antibody response, allowing enhanced viral replication and circulation for longer time periods, and enhancing the antitumor immune effect [168, 170]. Combination therapy with immunosuppressant agents has synergistic antitumor activity and appeared to overcome a pre-existing immunity without affecting metastatic tumor regression [115]. · Preclinical data in pancreas cancer: inhibition of the peritoneal dissemination of pancreatic cancer cells [118]; activity with intraportal administration [119]. · Phase I: IV Reolysin established as a safe therapy [220, 221]. · Phase I: ITu Reolysin in glioma [222] and advanced superficial malignancies safe [223]. · Phase I: Reolysin infused locally for 72 hours in patients with gliomas safe, 66% SD – one PR [224]. · Combinations with docetaxel [225], paclitaxel/ carboplatin [226] and gemcitabine [171] are well tolerated. · Clinical data for NSCLC, CRC, breast and pancreas cancers [120–122, 124, 227]. |
CRC: colorectal cancer, ITu: intratumoral, IV: intravenous, JNK: c-Jun N-terminal kinase, NFkB: nuclear transcription factor kappa B, NSCLC: non-small cell lung cancer, PKR: double-stranded RNA-dependent protein kinase, RNA: ribonucleotide nucleic acid, PR: partial response, SD: stable disease.