RE:RE:RE:CellPress: Emerging Field of OV Based Cancer ImmunotherapyFor further clarification ....
There are two types of hypoxic conditions. First, diffusion-limited hypoxia or chronic hypoxia leads to inhibition of cell proliferation in cancer regions with low oxygen concentration and the hypoxic microenvironment is a major limitation that affects the efficacy of many oncolytic viruses, other than reovirus (pelareorep)....The other form is acute hypoxia or perfusion-limited hypoxia, which is a temporary interruption in oxygen perfusion or fluctuation in oxygen level for several minutes. These hypoxic regions undergo cell death and create necrotic zones.
Jine X. et al. (2019) has shown that cancer cells adapting to hypoxia display a more aggressive phenotype and become more resistant to therapeutic strategies. A number of studies have shown that hypoxia may confer resistance directly or indirectly to conventional therapy, including radio-chemotherapy. Additionally, cancer stem cells located in the hypoxic niche of tumors involved in epithelia-mesenchymal transition (EMT) are naturally resistant to chemotherapy or radiotherapy. Radiotherapy demands sufficient oxygen to exert a cytotoxic effect on tumor cells; therefore, hypoxia could directly induce resistance to radiotherapy.
Some therapeutic agents, including cyclophosphamide, carboplatin, and doxorubicin, require oxygen to eradicate cancer cells. But reduced blood flow in acute hypoxia and greater diffusion distances, which are seen in chronic hypoxia, affect the distribution of such chemotherapeutic agents. Hypoxia can also indirectly decrease the effect of cancer therapies by regulating post-transcriptional and transcriptional gene expression. Such alterations in gene expression due to decreased oxygenation may lead to increased invasiveness, angiogenesis, metastasis, and drug resistance, all of which may reduce the efficacy of chemotherapy.