Barnes-Jewish Hospital | Washington University Physicians
breakthroughs from the lab


BY Julia Evangelou Strait

Liquid biopsies for colorectal cancer detect tumor DNA that has broken free of the cancer and is circulating in the blood.. Image courtesy of Science Photo / KTSDESIGN

Cancer is most often detected using traditional tissue biopsy: the removal of tissue by needle, endoscope or open surgery. The tissue sample is then examined for the presence of cancer cells. Though the standard of care, this kind of biopsy comes with some limitations. Because the procedure is invasive, it can be risky, and recovery can be uncomfortable. Additionally, such a procedure may not be safe for some people and may not be practical for those needing a series of biopsies to monitor the progress of cancer treatment.

According to the National Cancer Institute (NCI), “researchers have been exploring a new approach that could potentially complement or, in some cases, serve as an alternative to tissue biopsies.” That alternative is liquid biopsy, “which relies on analyzing bits of tumor material—molecules as well as whole cells—that are found in bodily fluids such as blood or urine.” While a few liquid biopsies have been approved by the Food and Drug Administration, mostly for lung, breast, ovarian and prostate cancers, none have been approved for colorectal cancer.

Following are reports of two new studies at Washington University School of Medicine that are assessing new applications for this relatively new cancer-care tool.

Liquid biopsy for colorectal cancer

A new study from a team of Washington University researchers demonstrates that a liquid biopsy examining blood or urine can help gauge the effectiveness of therapy for colorectal cancer that has just begun to spread beyond the original tumor. The test could detect lingering disease and serve as a guide for deciding whether a person should undergo further treatments to eradicate tumor cells that evaded initial treatment.

People who participated in this study had what is known as oligometastatic colorectal cancer, meaning each person’s cancers had spread beyond his or her original tumor but only to a small number of sites. Such patients undergo chemotherapy to shrink the new tumors before having surgery to remove whatever remains of the primary tumor. There is debate in the field about whether, after initial therapy, oligometastatic cancer should be treated like metastatic cancer, with more chemotherapy—or like localized cancer, with more surgery plus radiation at those limited sites.

That debate is further complicated by the fact that doctors have a limited ability to predict how people will respond to early chemotherapy. This is especially true because most patients do not have access to cancer genome sequencing, a process that identifies the specific DNA mutations in their original tumors.

“Being able to measure response to early chemotherapy without prior knowledge of the tumor’s mutations is a novel idea and important for being able to determine lab

whether the patient responded well to the therapy,” says Aadel Chaudhuri, MD, PhD, oncologist at Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, and senior author of the study. “This can provide guidance on how to treat oligometastatic disease. For example, if the liquid biopsy indicates that a patient responded well to the early chemotherapy, perhaps they should be offered the possibility of more surgery, which could potentially cure their disease. But if they didn’t respond well, it’s likely the cancer is too widespread and can’t be eradicated with surgery, so those patients should receive more chemotherapy to control their disease.”

Liquid biopsies for colorectal cancer detect tumor DNA that has broken free of the cancer and is circulating in the blood and, to a lesser extent, has collected in the urine. The study suggests that such liquid biopsies could help personalize treatment for oligometastatic colorectal cancer. Beyond identifying people at high risk of recurrence and helping guide decisions about which traditional therapies should be given, the new study also identified patients who might benefit from immune therapies and other targeted treatments.

“Based on mutations in the blood biopsy, we could identify patients who might benefit from a type of immune therapy called immune checkpoint inhibitors after their initial therapy is complete,” Chaudhuri says. “We also found mutations that could be targeted with drugs approved for other cancers. Our current study is observational, but it paves the way for designing future clinical trials that could test some of these potential therapies.”

The study findings were published online Feb. 12 in the Journal of Clinical Oncology Precision Oncology, a journal of the American Society of Clinical Oncology.

Liquid biopsy for metastatic prostate cancer

A blood test called EnhanceAR-Seq developed at Washington University School of Medicine, could help determine next steps for patients whose prostate cancer has spread despite treatment. This type of liquid biopsy is designed to help doctors determine if a patient’s disease can’t be effectively treated with a new therapy called androgen receptor (AR) targeted therapy. Knowing this, a patient could decide whether to pursue a more traditional, and potentially more beneficial, therapy.

“EnhanceAR-Seq predicted survival in metastatic prostate cancer patients who were treated with AR-targeted treatment,” Chaudhuri says. “Every single patient who was found to be positive by EnhanceAR-Seq developed treatment resistance, and unfortunately these patients were much more likely to die from their disease.”

Prostate cancer is the second leading cause of cancer death in American men, and it is estimated that one in every 41 will die of prostate cancer. The deadliest form of the disease is treatment-resistant metastatic prostate cancer, which grows despite treatment and may not be sensitive to drugs that target the androgen receptor pathway. One way to identify these high-risk patients is by tracking an alteration in the blood called AR-V7.

“Although noninvasive, this test has suboptimal sensitivity, meaning that it missed some patients with treatment-resistant metastatic disease,” Chaudhuri says. The study compared results from EnhanceAR-Seq with the AR-V7 blood test and showed that EnhanceAR-Seq was far more sensitive.

The researchers believe that their method, which requires a simple blood draw, could be made even simpler in the future. “Enhance AR-Seq could potentially be adapted to urine, too, something we are investigating in the lab,” Chaudhuri says.

The study’s findings were published online in JCO Precision Oncology, a flagship journal from the American Society of Clinical Oncology.

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