Bacteria Detects Cancer

An online advertisement for “new” cancer-detecting bacteria pops up on your screen. Bacteria are harmful, right? Why would anyone willingly introduce them into their body?

Cancer is a disease in which cells undergo uncontrollable cell division because of genetic mutations caused by a range of factors, including lifestyle, genetics, radiation, hormonal changes, and infections. For instance, mutated versions of the BRCA1 and BRCA2 genes lead to a higher risk of breast cancer. Cancer leads to the formation of tumors, which are abnormal tissue growths through which the disease is often first discovered. These tumors can be malignant (harmful) or benign (harmless). However, tumors can change from benign to malignant if they continue to divide uncontrollably. This sudden switch in proliferation is caused by either a mutation, change in gene expression, or immunodeficiency. Cancer has the ability to metastasize—spread to other parts of the body.  The extent to which a cancer has metastasized is used to define its stage. Typically, cancer has four stages (stage I is early growth & stage IV the full metastasis of the tumor), but it can also have a stage zero. This stage indicates that the cancer is still small and located at its original point. Since cancer is the second highest cause of death worldwide, research on its causes and treatment has been extensive. Traditional treatments like chemotherapy and surgery are slowly being replaced by more precise methods such as stem cell transplants and precision medicine. Despite the extensive research and resources dedicated to cancer, a cure has eluded the scientific community for years.

However, a new discovery has revolutionized the way medical professionals can detect cancer by cleverly using bacteria, an idea that was never tested before. Sometimes, tumors do not reveal themselves easily and can cause multitudes of problems by the time they are discovered in a fully developed stage. The use of bacteria that can travel inside a patient (without requiring imaging) allows for complete surveillance of the targeted site, aiming to solve this issue. Jeff Hasty, a professor at the University of California, San Diego School of Biological Sciences and Jacobs School of Engineering, proposed “Cellular Assay for Targeted CRISPR-discriminated Horizontal gene transfer,” or CATCH. 

Using CRISPR, researchers were able to edit a bacterial genome to look for DNA particles emitted from tumors. As tumors multiply rapidly, they eventually die and release DNA into the bloodstream. A specific genetically-modified gut bacteria, Acinetobacter baylyi, was used as a case study for this experiment because it is an excellent model for genetic engineering and has the ability to intake DNA from its surroundings easily (i.e. natural competence). Since this bacteria is found in the gut, they experimented with finding colorectal tumors in mice. These tumors were known to usually have mutated KRAS genes, so the team rigged up the bacteria (using CRISPR) to intake DNA containing the common KRAS mutation G12D. The KRAS gene produces a protein, K-Ras, used in a part of a signaling pathway known as the RAS/MAPK pathway. This pathway is responsible for sending signals in and out of the cell and for cell proliferation. 

For the first experiment, they tested the bacteria on colorectal cancer cells in vitro. The bacteria was able to incorporate the DNA fragment into their own genomes, which was shown through genomic analysis. Then, they decided to test the bacteria in vivo in the guts of mice with and without colorectal cancer. They partially succeeded with both positive and negative results. The team extracted the bacteria from the mice and grew them on petri dishes, applying specific usage of antibiotics to grow only colonies with bacteria containing cancer DNA. Cancer-bacteria did grow, with genomic analysis further confirming the results. However, there were both false-positives and false-negatives seen in the mice, but never in the lab dish. The team believes that this is an overcomable obstacle and that further research will be required to resolve it.

Despite their microscopic size, bacteria play a key role in medical innovation. Their ability to detect cancer with some degree of accuracy is an impressive feat in itself. Given the extreme diversity of bacteria, this method can be expanded and applied to the detection of other cancers. The findings of the experiments also suggest that, with further use of CRISPR, genetically-modified bacteria might be able to directly treat cancer or prevent the spread of it. With new research, engineered bacteria might possess the ability to restrict tumor growth or even create proteins to stop metastasis. In the future, with the advent of new technologies, the process of detecting cancer might come down to a tiny bacterial cell.