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Engineering probiotics for early detection and interception of ovarian cancer
Synthetic biology is driving a new era of medicine through the genetic programming of living cells. This transformative approach allows for the creation of engineered systems that intelligently sense and respond to diverse environments, ultimately adding specificity and efficacy that extends beyond the capabilities of current approaches. Due to recent studies indicating the prevalence of bacteria within the human body and specifically in tumor tissue, bacteria have generated significant interest as cancer therapeutics and diagnostics. Additionally, a multitude of empirical studies have demonstrated that administered bacteria selectively grow in tumors due to reduced immune surveillance of tumors. Given their presence in ovarian cancer patient tissues, and selectivity demonstrated in ovarian cancer mouse models, bacteria present a unique opportunity to be engineered as smart delivery vehicles for cancer detection and interception.
Our proposal aims to engineer probiotic bacteria for the early detection and interception of serous tubal intraepithelial carcinoma (STIC) lesions, an early step in the development of high grade serous ovarian cancer (HGSOC). In this approach, probiotic bacteria will be administered selectively to STIC lesions. Acting as a microbial ‘Trojan horse’, probiotics will be designed to locally produce high concentrations of genetically-encoded molecules. This includes a small molecule that can be easily detected in the blood or urine, offering a non-invasive diagnostic method. Additionally, probiotics will be engineered to produce a therapeutic molecule for cancer interception, which can reduce toxicities and immune-related adverse effects compared to other delivery approaches. If successful, this approach has the potential to advance early detection and interception for ovarian cancer.
December 7, 2023