VEGFA and metastatic neoplasm: Since phytochemicals and their synthetic derivatives often protect the cardiovascular system from chemotherapy induced damage (248, 263, 264), we propose, as a first-line therapy for difficult and metastatic tumors, to pretreat with phytochemicals or synthetic derivatives, then continue treatment and add sequentially a VEGF blocker, ICBs, and chemotherapy (to trigger the immunogenic cell death).