In CRC, the importance of hypoxia-induced VEGF overexpression within the TME in driving chemoresistance is demonstrated by the finding that downregulation of HIF-1α expression overcomes the hypoxia-induced chemoresistance to oxaliplatin trough the reduction of VEGF levels and the inhibition of angiogenesis in a CRC mouse model [38]. The gene discussed is HIF1A; the disease is colorectal carcinoma.