Liquid biopsies may aid diagnosis, treatment of bladder, nerve tumors – Washington University School of Medicine in St. Louis
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Blood and urine biopsies could pave the way for more personalized cancer therapy
Blood and urine tests could lead to faster and less invasive methods of diagnosing and monitoring different types of tumors, new research shows. Two studies led by Washington University School of Medicine in St. Louis describe the potential of liquid biopsies to identify and track tumor growth in two very different cancers: bladder cancer and peripheral nerve tumors. Despite the differences between these cancers and the associated biopsies, the studies show the potential benefits of this relatively new tool in the fight against cancer.
Both studies appear in the Aug. 31 issue of PLOS Medicine, a special issue of the journal devoted to liquid biopsies.
One study reports the development of a urine biopsy to check for bladder cancer. With an easy-to-collect urine sample, doctors were able to determine whether the first treatment had eradicated the cancer or whether any remnants of the disease remained. This knowledge can lead to fewer patients undergoing unnecessary operations. The second study describes a blood biopsy to diagnose a tumor of the sheath — or lining — covering peripheral nerves. This rare cancer is caused by an inherited genetic condition called neurofibromatosis type 1 (NF1). In patients with NF1, it is difficult to determine whether tumors that develop in the nerve sheath are benign or malignant.
“Our studies show how cancer management can improve with liquid biopsies that accurately diagnose and track tumors at different stages of the disease,” said Aadel A. Chaudhuri, MD, PhD, an assistant professor of radiotherapy and the senior author of both papers. . Chaudhuri also treats patients at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.
“For bladder cancer, if a urine biopsy can detect whether the early chemotherapy has completely eradicated the tumor, it may help some patients avoid major surgery to remove the bladder,” he said. “And for NF1, if we can differentiate between cancerous versus precancerous tumors, we open the door to early detection of cancer in inherited conditions that predispose people to developing cancer.”
Patients with bladder cancer that has invaded the underlying muscle typically undergo chemotherapy to shrink the tumor, followed by surgery to remove the bladder. Bladder removal, which may also include removal of the prostate and seminal vesicles for men, and removal of the uterus, ovaries, and part of the vagina for women, reduces the risk of the cancer coming back. But some patients may respond well to initial chemotherapy and may not need to have the bladder or nearby organs removed. Unfortunately, today there is no way to determine which patients may not need to undergo bladder removal, a procedure that has a major impact on quality of life. The urine biopsy that Chaudhuri and his colleagues performed could provide a way to determine which patients can safely avoid bladder removal in the future.
In the study, the researchers analyzed DNA found in the urine of healthy people and bladder cancer patients treated with chemotherapy. After chemotherapy, but before surgery to remove the bladder, the scientists were able to identify residual tumor DNA in the urine of cancer patients that would otherwise go undetected. All patients underwent surgery to remove the bladder. The researchers found tumor DNA in the urine of patients in whom it was later found that the bladder still had residual tumor after chemotherapy. In contrast, those patients who had so-called complete responses to the chemotherapy — no evidence that tumors remained in the bladder after it was surgically removed — also showed no tumor DNA in their urine prior to surgery.
While the test is not yet sensitive enough to guide treatment decisions, Chaudhuri said the study paves the way for further refinement of the test toward identifying patients who can keep their bladders after chemotherapy.
Co-corresponding authors on the urine biopsy for bladder cancer are Vivek K. Arora, MD, PhD, an assistant professor of medicine; and Zachary L. Smith, MD, an assistant professor of surgery, both at Washington University School of Medicine. The co-first authors are Pradeep S. Chauhan, PhD, a staff scientist; Kevin Chen, a medical student; Ramandeep K. Babbra, MD, a research assistant; and Wenjia Feng, a research assistant, all in Chaudhuri’s lab.
Patients with NF1 are prone to developing cancer, and tumors of the peripheral nerve sheath are the most common cause of death for such patients. These cancers usually arise from benign tumors and it is often difficult to distinguish between the benign and malignant forms of these tumors.
Chaudhuri worked with Angela Hirbe, MD, PhD, an assistant professor of medicine in the Division of Medical Oncology and director of the Adult NF Clinical Program, and Jack Shern, MD, the Lasker Clinical Research Scholar in the Pediatric Oncology Branch at the National Cancer Center for Cancer Research of the Institute. Together they developed a method to analyze the DNA in a blood sample that can distinguish between healthy individuals, NF1 patients with benign tumors and NF1 patients with malignant peripheral nerve sheath tumors. The DNA analysis also correlated with how well the patients responded to treatment.
In the future, the liquid biopsy could help doctors determine when benign tumors in NF1 patients become malignant, improving early cancer detection and early treatment in patients at high risk of developing cancer.
The co-first authors of this study are Jeffrey J. Szymanski, MD, PhD, a bioinformatics scientist at Washington University, and R. Taylor Sundby, MD, of the National Cancer Institute’s Center for Cancer Research.
While these two liquid biopsies demonstrate the technology’s utility and versatility for vastly different tumors, Chaudhuri is expanding his team’s research beyond cancer. He recently received a five-year grant of $1.97 million from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) to develop a liquid biopsy to diagnose and monitor sepsis, a life-threatening reaction. for infection that causes inflammation throughout the body.
The biopsy work for bladder cancer was supported by the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS), grant number TL1TR002344; the Radiological Society of North America (RSNA) Medical Student Research Grant; the Midwestern Stone Institute; the Rabushka Bladder Cancer Research Fund; the Damon Runyon Clinical Investigator Award; the Alvin J. Siteman Cancer Research Fund; the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS), grant number UL1TR002345; the National Cancer Institute (NCI), grant number K08CA238711; the Young Investigator Award from the Cancer Research Foundation; and the V Foundation V Scholar Award.
Chauhan PS, et al. Urinary tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative radical cystectomy: a prospective cohort study. PLOS Medicine. August 31, 2021.
The tumor biopsy work of the peripheral nerve sheath was supported by the Children’s Cancer Foundation NextGen Award; the National Institute of General Medical Sciences, grant number 5T32GM007067; the Center for Cancer Research Flex Award; the NCI Center for Cancer Research Intramural Research Program, grant numbers 1ZIABC011722-04 and 1ZIABC010801-13; the Francis S. Collins Scholars Program in Neurofibromatosis Clinical and Translational Research; the National Cancer Institute, grant number 1K08CA238711; the Cancer Research Young Investigator Award; and the V Foundation for Cancer Research.
Szymanski JJ, et al. Cell-free DNA ultra-low-pass whole genome sequencing distinguishes malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion. PLOS Medicine. August 31, 2021.
With respect to both projects, Chaudhuri reports the following competing interests: He has patent applications related to cancer biomarkers and has served as a consultant/advisor to Roche, Tempus, Geneoscopy, NuProbe, Daiichi Sankyo, AstraZeneca, Fenix Group International and Guidepoint. He has stock options in Geneoscopy, research support from Roche and ownership interests in Droplet Biosciences.
The 1,700 faculty physicians of Washington University School of Medicine are also the medical staff of the children’s hospitals of Barnes-Jewish and St. Louis. The School of Medicine is a leader in medical research, education, and patient care, consistently ranked among the top medical schools in the nation, according to US News & World Report. Through its ties to Barnes Jewish and St. Louis Children’s Hospitals, the School of Medicine is affiliated with BJC HealthCare.