Instead of relying of invasive procedures requiring tissue samples, doctors would simply use a blood or urine sample to identify the presence of a mutation and monitor response to therapy. Aside from use in screening, these types of tests may also help people already fighting the disease since doctors can choose treatments based on the specific DNA mutations the test identifies.
Testing for KRAS Mutations
Liquid biopsy testing is a promising avenue of research in patients with pancreatic cancer, as well as those with other solid tumor cancers such as lung, breast, melanoma, and colorectal, among others.
One liquid biopsy test currently available is Trovera, from Trovagene, a San-Diego, California-based molecular diagnostics company. This noninvasive test measures circulating tumor DNA (ctDNA) shed into the bloodstream by growing tumors. This ctDNA can potentially provide vital information on tumor progression and treatment effectiveness.
An estimated 90% of pancreatic cancers harbor somatic KRAS G12/G13 mutations. These mutations are hallmarks of late-stage disease, and the presence of circulating tumor DNA (ctDNA) KRAS mutations at diagnosis has prognostic implications. Accurate identification of both the presence of ctDNA KRAS mutations and quantification of the number of ctDNA KRAS mutant copies could be an improved therapeutic response biomarker over CA 19-9, which is known to be uninformative in certain patients with pancreatic cancer.
A Blood or Urine-Based Biopsy
Trovera is unusual in that patients have a choice between a liquid biopsy based on a simple blood draw, or a biopsy based on urine, explains Victoria Raymond, director of medical and scientific affairs at Trovagene.
“Our scientists were the first to discover that ctDNA is released into the urine as well as the bloodstream,” says Raymond, adding that a urine test can be collected by the patient, without the need for a trip to their doctor’s office. “Everything is done by physician order, but a patient has the option of not making a visit to the provider’s office, which can be very helpful to people who are recovering from treatment or have long trips to a doctor’s office.”
The patient would simply collect the urine sample in the urine collection kit provided and send it to Trovagene’s CLIA lab for analysis.
On the other hand, a patient who is in the doctor’s office for a blood test for CA19-9 can have blood drawn for the Trovera KRAS liquid biopsy test too. “It’s really about providing people options and getting a doctor information more quickly,” Raymond says.
Early Studies Show Promise
In May, the company presented data at the 2016 AACR Special Pancreatic Cancer Meeting in Orlando, Florida. The poster presentation, “Detection and Quantification of ctDNA KRAS Mutations from Patients with Unresectable Pancreatic Cancer,” showed some promising results.
Highlights from the poster include:
- Detection rate of circulating tumor DNA (ctDNA) KRAS in 210-patient study closely matches the published prevalence of KRAS mutations in pancreatic cancer (~90%).
- ctDNA KRAS levels can be used to distinguish between locally advanced and metastatic cancer (p<0.0001), suggesting an improved biomarker for disease differentiation.
- Longitudinal monitoring of KRAS can be informative in determining responsiveness to therapy and to predict disease progression months in advance of imaging.
Currently, Trovagene is partnering with several high-profile pancreatic cancer experts from the University of Michigan, MD Anderson Cancer Center in Texas, Arizona-based Honor Health, and University of California, San Francisco, among others. The company’s urine and blood-based assay has been selected by the Pancreatic Cancer Action Network as the liquid biopsy provider to participate in Precision Promise, the first large-scale precision medicine trial designed to transform outcomes for patients with pancreatic cancer.
“We’re very hopeful about this, but of course larger-scale studies need to be done,” says Raymond. “The ultimate goal is to advance the treatment of pancreatic cancer, and the way to do that is to publish the data and get that data in front of the experts who ultimately influence treatment.”