# Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment
## 3 Conventional Cancer Therapy in Combination with Bacteriotherapy  
The conventional modalities of cancer treatment such as chemotherapy, radiotherapy, and surgery have been used extensively. However, the chances of systemic toxicity, metastatic potential, development of secondary tumors, and possibilities of drug resistance may lead to ineffective treatments [120; 121]. The chemotherapeutic agents encounter issues like poor tumor targeting, inadequate tumor penetration, and low cytotoxicity to cancer cells. Further, tumor hypoxia reduces the sensitivity of tumors to ionizing radiation and chemotherapeutics [122]. To counter these obstacles, integration of the conventional modalities of treatment with bacterial cancer therapy can introduce new approaches for achieving better clinical outcomes. Bacteriolytic _Salmonella_ therapy in conjunction with cyclophosphamide decreased tumor vascularization and suppressed the tumor in melanoma model [123]. [PERSON] et al. investigated the effect of _Salmonella_ (LVR01 attenuated strain) in conjunction with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy in non-Hodgkin lymphoma bearing mice. Enhanced immune response was observed due to large influx of immune population, increased chemokines, proinflammatory cytokines, and activation of NK cell cytotoxicity. The combination of Salmonella immunotherapy demonstrated profound immune response and greater tumor activity than the CHOP therapy alone [124]. The _C. novyi_-NT spores in combination with microtubule interacting drugs such as vinorelbine and docetaxel demonstrated tumor regression in colon cancer xenograft models (HCT116). The combination therapy led to the destruction of both, the vascular and avascular components of the tumor [125]. In a recent study by [PERSON] et al., the authors observed that immunotherapy provided by _Salmonella typhimurium_ in combination with low dose doxorubicin, reduced the tumor burden in murine breast cancer model. The combination showed greater tumor reduction and lower toxicity than either therapy alone [126]. [PERSON] et al. devised paclitaxel liposomes and internalized them in bacteria (known as paclitaxel-in-liposome-in-bacteria, LPB) _E. coli_ and _L. casei_ for the treatment of lung cancer. The intratracheal administration of these bacterial formulations led to the enhanced immune cell migration (neutrophils and leucocytes) into the tumor microenvironment and the lung tumor tissues showed higher levels of TNF-\(\alpha\), IL-4, and IFN-\(\gamma\) than healthy lung tissues. The synergistic effect of the immunostimulation and high drug distribution of paclitaxel in the lungs resulted in successful anti-tumor effect [127]. To explore the combination of bacterio- and radiotherapy, _Salmonella_ strain VNP20009 was coated with photothermal agent, polydopamine. The bacteria aids in the penetration of the photothermal agent to the core hypoxic region of the tumor and the biomimetic polydopamine on the surface of the bacteria aids in the conversion of near-infrared light into heat which causes tumor ablation in mice bearing malignant melanoma. The photothermal therapy kills tumor cells and generates cell lysates, which act as antigens to generate immune response and promotes bacterial growth. The tumors were eliminated and no relapse or metastasis was observed after one injection and irradiation [128; 129]. Intratumoral administration of _Pseudomonas aeruginosa_ in combination with localized low frequency square pulsed magnetic field exposure was effective in Ehrlich tumor treatment. Limited bacteria related toxicity and limited tissue injury contributed to the effectiveness of this combination [130]. Branched gold nanoparticles coated with _C. novyi_ NT were fabricated and used with computed image tomography for delivery in prostate cancer mouse models [131].