Fig. 4.

A genetically engineered bacterium can overcome the multifactorial challenges of drug resistance. The bacteria can actively target the tumor site without producing the anticancer compound, reducing off-site toxicity. After reaching the tumor, the bacteria can burrow past the extensive ECM into the hypoxic tumor core. Once the bacteria has colonized the tumor, genetic switches activated by quorum sensing or the tumor microenvironment produce multiple therapies that target parallel disease pathways resulting in complete tumor elimination.