Technique using urine suggests individualized bladder cancer treatment possible
A research team, led by investigators from Georgetown University Medical Center and Fudan University in China, has devised a very promising non-invasive and individualized technique for detecting and treating bladder cancer.
The method uses a “liquid biopsy” — a urine specimen — instead of the invasive tumour sampling needed today, and a method developed and patented by Georgetown to culture cancer cells that can reveal the molecular underpinnings of each patient’s unique bladder cancer.
Their study sets forth a cost-friendly, simpler and painless technique that can determine the best treatment for each person’s bladder tumour, monitor the progress of that treatment, predict or detect cancer recurrence early, and identify new drugs that are sorely needed for this common cancer.
“This is the first study to show, using patient samples, that a ‘living liquid biopsy’ from urine can help determine treatment. This work also suggests that we might be able to grow and test cancer cells for treatment from other ‘living biomarkers’ found in blood and saliva. We are just at the beginning of this new diagnostic innovation,” says study co-senior author Xuefeng Liu, MD, professor of pathology and oncology and member of the Center for Cell Reprogramming at Georgetown University and Georgetown Lombardi Comprehensive Cancer Center.
The ability to use a patient’s urine to grow cells is a transformational innovation from Georgetown called “conditional reprogramming,” or CR. Patient-derived cells using CR can grow indefinitely without genetic manipulation, says Liu. Before this technique, which is less than a decade old, normal cells could not grow in lab culture, and cancer cells acquired numerous genetic mutations using previous culturing techniques.
“The analysis of the mutation ratio for both patient tissue and corresponding CRC confirmed that both single nucleotide variants and DNA insertions and deletions were retained during the culturing,” says Liu.
This means that a patient’s urine produced cancer cells that molecularly matched their cancer tissue sample. “We also identified some mutations not identified in the original tumour biopsies, suggesting that the urine cell cultures better reflect overall tumour diversity than a single biopsy,” he says. “The CRC technique may also expand our understanding of how low frequency mutations help lead to bladder cancer development and progression. Overall, CRC cultures may identify new actionable drug targets and help explain why this cancer is so often resistant to treatment.”
After determining that the urine colonies and tumour tissue samples had matching molecular characteristics and genetic alterations, the researchers tested urine-based CRC cancer cells with 64 clinical oncology drugs. They found that, overall, the urine-based cancer cells were resistant to more than half of the drugs. And they discovered that many of the urine cancer cells were highly sensitive to one of the drugs, bortezomib, which is currently being tested for a different genitourinary tumour, urothelial cancer.
Georgetown University Medical Center
https://tinyurl.com/y46httzz