HIF1A and neoplasm: This genetic modification improved the replication of the virus in hypoxia.[57] Hypoxia‐inducing factor 1 (HIF‐1α) is an essential factor in hypoxia that can enhance angiogenesis and tumor cell metastasis.[58] Moreover, it has been reported that HIF‐1α improves HSV‐1 proliferation.[59, 60] In contrast, HIF‐1α and the expression of its target genes are negatively regulated in hypoxic conditions by the Newcastle disease virus.[61] Tumor resistance to oncolytic viruses is another problem with virotherapy.