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Cancer blood tests getting closer to tissue biopsies in results

One of the next big advances in cancer treatment will be the development of blood tests, called liquid or blood biopsies, that can monitor the growth of tumors by analyzing DNA shed from tumors into the bloodstream, several cancer experts tell Axios. Multiple research facilities and biotech companies are developing and testing these biopsies, but before they’ll be seen in the clinic they need to lower the costs and prove the tests are reliable and lead to patients living longer.

The bottom line: The blood tests could help determine more precise treatments for cancers proven stubbornly hard to treat, like brain cancer. “In my opinion, there is very little doubt it will be” available soon, said Mark Roschewski, a staff clinician at the lymphoid malignancies branch at the National Cancer Institute. “Only question is when and at what breadth.”

 

Where it stands: A significant amount of cancer research is now about fine-tuning the testing, lowering the genetic sequencing costs, and proving the clinical worth, Roschewski says. Shiuh-Wen Luoh, a medical oncologist at Oregon Health and Science University, agrees: “For today and tomorrow, it may stay in the academic arena.”

The NCI is facilitating that effort with an initiative to advance the development and validation of liquid biopsytechnologies. The institute aims to create a public–private partnership for engineers and clinical experts to work together.

Here’s what cancer experts say about the benefits of liquid biopsies and where things stand:

Pros:

  • Blood tests are much less invasive, easier to conduct, and safer than a tissue biopsy.
  • The blood tests can be taken routinely during treatment, which is particularly important as tumors change over time.
  • By watching how tumors evolve, therapeutic approaches could be more targeted to the patient’s specific cancer.
  • They may be used for tumors in places where it is difficult to access, like the brain.
  • They can pick up minute fragments of tumor DNA earlier than a CT scan can see a physical tumor. Once a tumor is eradicated, the DNA fragments from that tumor will clear out as soon as a few days later, so the blood test could be a good method of checking on the patient’s status.
  • Blood biopsies may also be good for testing the effectiveness of a particular medicine.
  • Blood can contain a range of gene fragments that could provide a broader perspective of the various tumors, whereas a tissue biopsy only shows the genetic coding in that particular part of that particular tumor.
Cons:
  • False positives may cause a patient to undergo unnecessary and painful treatments.
  • There is a lack of research showing patients live longer or avoided chemo. (Note: Expect some studies on this soon.)
  • Blood tests aren’t currently as reliable as a tissue biopsy, but the study noted below shows it is getting closer.
  • The technology is not sensitive enough to track all of the tumor changes.
  • Costs remain high. “Sequencing and analysis costs drive the expense of these analyses,” said Harvard University’s Keith Flaherty.
 

What’s new: A team of scientists this week announced a new approach for monitoring metastatic cancer DNA from blood samples that shows nearly 90% of the genetic features of a tumor can be detected in blood by sequencing all of the protein-coding genes (something known as whole-exome sequencing).

What they found: Their approach was effective for up to 49% of patients with advanced cancer. (It involves a two-step process of first screening potential participants and then running the whole-exome sequencing on those with 10% DNA in their blood sample.)

In order to screen the participants, the team first developed a new tool, called ichorCNA, which they used to. test 1,439 blood samples collected from 520 metastatic breast and prostate cancer patients.

Study author Viktor Adalsteinsson says ichorCNA is one way that costs for blood biopsies can be lowered because it ensures the right type of sequencing is applied to each sample, based on its tumor content.

Why this is important: Cancers respond differently in each person, and tumor DNA analysis may help to unravel what might work for a particular patient.

We can now look not only gene-by-gene but throughout the entire cancer genome in order to figure out which treatments are right for which patient, and why some cancer cells don’t respond to therapy. Doing so may inform better ways to treat the entire cancer and to prevent it from coming back,” Adalsteinsson says.

Harvard’s Flaherty, who was not part of the study, agrees. “The most astounding and important finding of this study is that tumors shed enough DNA into the bloodstream to permit an entire genomic profile to be generated. Just a few years ago, it was thought that this level of molecular analysis would only be possible by obtaining a sample of a tumor.”

What’s next: Luoh points out the study showed whole-exome sequencing only applies to one-third of metastatic patients, but there are new efforts to sequence even more minute amounts of DNA.

“If an approach like the one described in the Adelsteinsson paper could be made more sensitive then cancer could not only be detected earlier, but its molecular features could be ascertained at that same time and the appropriate therapy assigned,” Flaherty said.

The big picture: NCI has a deep dive into how liquid biopsies are currently used to detect, track and treat cancer.

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