Factors that affect MMP and confer radiosensitivity are, to take a few examples, growth differentiation factor-15 (GDF15) belonging the TGF-β superfamily, which may represent a target to radiosensitize head and neck cancer cells by reducing MMP activation and allowing ROS generation; inhibitors of MEK/ERK-mediated signaling, such as PD98059, which increase MMP and FAS-mediated cell death (and caspase-8 activity); inhibitors of histone deacetylase reduce MMP and increase ROS generation together G2/M phase cell cycle arrest with apoptosis in esophageal cancers. This evidence concerns the gene CASP8 and head and neck cancer.