# Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment
## 2 Mechanism of Tumor Suppression
### Genetically Engineered Bacteria for Anti-Cancer Therapy
#### 2.2.4 Drug Expression Strategies  
Bacteria can sense and respond to a variety of stimuli. This property is often exploited for production of anti-cancer entities such as genes encoding for immune modulating agents and enzymes specifically at the tumor site [62]. \begin{table}
\begin{tabular}{c c c c c c} \hline
**Treatment Strategy** & **Bacterial Strain** & **Gene/Drug** & **Mechanism of Action** & **Application** & **References** \\ \hline \multirow{3}{*}{Prodrug Therapy} & \multirow{3}{*}{_Salmonella_} & Thymidine kinase & \multirow{3}{*}{Inhibits deoxyguanosine triphosphate, dGTP,} & \multirow{3}{*}{Melanoma} & [63] \\  & & polypeptide & & incorporation into DNA & \\ \cline{3-5}  & & Prodrug: Gancidovir & & & \\ \hline \multirow{3}{*}{Prodrug Therapy Anti-Angiogenic Therapy} & \multirow{3}{*}{_Escherichia Cali_} & Uridine phosphoryylase & \multirow{3}{*}{Impede thymidylate synthase enzyme} & Colon, rectum, and head and & [64] \\  & & Prodrug: Capsetabine & & neck cancers & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \hline \multirow{3}{*}{Prodrug Therapy Anti-Angiogenic Therapy Anti-Angiogenic Therapy Immunotherapy} & \multirow{3}{*}{_S. typhimurium SL7207_} & \multirow{3}{*}{VEGF-2} & Upregulates vascular-endothelial growth factor receptor 2 (FLR-1) of proliferating endothelial cells in the tumor vasculature & Melanoma, Colon carcinoma, Lung carcinoma, & [66] \\  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \hline \multirow{3}{*}{Anti-Angiogenic Therapy Immunotherapy Quorum Sensing peptides for anti-tumor action} & \multirow{3}{*}{_Listeri_} & \multirow{3}{*}{Listeriolysin O} & Releases proinflammatory cytokines and increases expression of co-stimulant molecules in antigen presenting cells surfaces leading to maturation and activation of high affinity T cells & Prostate cancer & [69] \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \hline \multirow{3}{*}{Biofilms as Anti-Cancer Agents} & \multirow{3}{*}{_Striptoccoccus agalactaire_} & \multirow{3}{*}{Polysaccharides} & \multirow{3}{*}{Inhibit adhesion of cancer cells to endothelial cells} & \multirow{3}{*}{Colon cancer} & [71] \\ \cline{3-5}  & & & & & \\ \cline{3-5}  & & & & & \\ \hline \end{tabular}
\end{table} 
Table 2: Applications of genetically engineered bacteria as vectors for anti-cancer treatment. The control on gene expression is critical for delivery of therapeutic payload at the tumor site, especially to ensure that the remaining healthy cells are unaffected. Specificity can be achieved by inserting therapeutic agents under the control of promoters which are induced by factors such as hypoxia or radiation. Further, the gene expression can be regulated by externally inducible promoters (like chemical compounds -L-arabinose) or microenvironment sensing promoters (like \(\gamma\)-irradiation) [62]. Bacteria reside in close communities and communicate internally using signaling molecules. This mode of communication is referred to as quorum sensing (QS). The regulation of gene expression can also be controlled by these QS molecules [72]. The application of QS phenomenon in cancer treatment has been discussed in detail in Section 2.6. [PERSON] et al. employed the fumarate and nitrate reduction (FNR) regulator in _Salmonella typhimurium_ for expression of gene encoding for cytolysin. The FNR dependent promoter is highly sensitive to oxygen and activates gene expression under anaerobic conditions hence, making it suitable for hypoxic tumor regions. The _S. typhimurium_ equipped with FNR dependent promoter demonstrated successful expression of the genes encoding for cytolysins in mammary tumors and resulted in reduced tumor growth [73]. Light inducible promoters are used for spatiotemporal modulation of gene expression.