Cancer chemotherapies suffer from the development of drug resistance and a lack of specificity of treatments. In particular, pancreatic cancer mortality rates remain high, with a low probability of long-term survival and is thus the focus of the current proposal. Spontaneous tumor regression following a severe microbial infection was observed over 150 years ago and inspired some of the earliest cancer therapies. Evidently, a bacterial infection in a cancer patient stimulates the immune system to trigger robust anti-tumor immunity in the otherwise immune-suppressive tumor microenvironment. Salmonella has emerged as an ideal therapeutic candidate due to its intrinsic tumor targeting ability an...
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Cancer chemotherapies suffer from the development of drug resistance and a lack of specificity of treatments. In particular, pancreatic cancer mortality rates remain high, with a low probability of long-term survival and is thus the focus of the current proposal. Spontaneous tumor regression following a severe microbial infection was observed over 150 years ago and inspired some of the earliest cancer therapies. Evidently, a bacterial infection in a cancer patient stimulates the immune system to trigger robust anti-tumor immunity in the otherwise immune-suppressive tumor microenvironment. Salmonella has emerged as an ideal therapeutic candidate due to its intrinsic tumor targeting ability and its direct or immune-mediated anti-tumor effects. More studies and new models are needed to identify the underlying mechanisms that contribute to colonization at the tumor site by Salmonella as well as its anti-tumor benefits. The use of bacterial therapy fell out of favor as chemotherapy approaches were subsequently developed. The proposed research will develop new strategies for cancer treatment that take advantage of the innate ability of Salmonella bacteria to target tumors and promote tumor regression. These studies employ in vitro models of tumors (referred to as spheroids) and a novel chick embryo xenograft model (the chick allantoic membrane or CAM model) combined with state-of-the-art imaging to decipher the steps that bacteria employ to colonize tumors and drive regression. Identification of the mechanisms involved will enable us to engineer mutant strains that can eradicate specific tumors or deliver tumor-associated antigens without causing infections in patients.
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