Genetic Engineering, Salmonella and Brain Tumors

By Janet Taylor

 

Glioblastomas are tumors that form from the astrocytes in the brain. These tumors are aggressive and lethal largely because they can be composed of multiple types of tissues and because the brain provides such a large blood supply, which helps them to grow. While they rarely invade the body outside of the brain and spinal cord, they inflict their damage quickly. Patient survival is an average of two years, while those with more aggressive types are given a life expectancy of about fifteen months. The standards for treatment consist of surgery plus chemo or radiation but recurrence occurs quite often and because there are multiple cell types in each tumor, targeted therapy isn’t successful. Genetic biomarkers have been investigated to identify tumor changes as well as why some patients respond better than others with the same treatments. While several have been identified, their utility has yet to be seen for predictive factors or treatment alternatives.

 

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Researchers at Duke University have taken an alternative approach to fighting this disease using genetically engineered Salmonella typhimurium. The bacteria contain a mutation that depletes their purine stores. Since tumor cells are loaded with purine, the Salmonella would be expected to seek out those tumors. Once inside the tumor, they rapidly reproduce. Second, the addition of a p53 tumor suppressor protein and Azurian allows the bacteria to self-destruct inside the tumors without eliciting an immune response. The bacteria have been programmed to operate efficiently in hypoxic, purine rich environments only so the tumor is destroyed but local, healthy tissue remains unharmed.

 

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Their research showed that rats with extreme cases of glioblastoma had a 20 percent survival rate, with the tumors going into remission over a period of 100 days. There is no indication as to  when this could move from mice to men, but the results show promise for better outcomes from this deadly cancer.

 

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References

American Brain Tumor Association, http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html

McNamara MG, Sahebjam S, Mason WP. Emerging Biomarkers in Glioblastoma. Cancers. 2013;5(3):1103-1119. doi:10.3390/cancers5031103.

Mehta, N., Lyon, J. G., Patil, K., Mokarram, N., Kim, C., & Bellamkonda, R. V. (2017). Bacterial Carriers for Glioblastoma Therapy. Molecular Therapy – Oncolytics, 4, 1-17.

doi:10.1016/j.omto.2016.12.003                          

http://www.pubcan.org/printicdotopo.php?id=4938

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