TLR4 and cancer: Of note, picibanil (a lyophilized preparation of Streptococcus pyogenes that operates as a TLR2/TLR4 agonist has been licensed for use in cancer patients by the Japanese Ministry of Health and Welfare (but not by the US FDA) as early as in 1975 [428, 429]; while mifamurtide (a synthetic lipophilic glycopeptide that activates NOD2) has been approved by the EMA for the treatment of osteosarcoma in 2009 [430-432].