More signal, less noise
GRAND FORKS, N.D. – Talking epigenetics, Dr. Motoki Takaku mused from his office at the UND School of Medicine & Health Sciences (SMHS) that studying what’s happening inside a cell is a bit like tuning a radio: there’s signal, and there’s noise.
Sometimes a lot of noise.
And all too often, he said, this noise interferes with researchers’ ability to see cellular functions clearly – at least at the genetic level.
“We’re trying to improve our ability to identify these signals so that our precision will be much higher,” explained Takaku of his efforts to develop better DNA-based biomarkers and treatments for cancer. “If we can make these signals much cleaner, that will eventually lead to more confident diagnoses.”
Cell-free DNA
Fortunately, for both providers and patients, that work is finally getting at least a bit easier, Takaku said, not only due to evolving technologies in the science of epigenetics, but through the study of something called cell-free DNA (cfDNA).
Cancer is the result of genetic changes within cells and tissues, of course. When the altered cells that produce cancer are released by a tumor and enter the bloodstream, though, cancer can metastasize or spread. But even when cancer doesn’t metastasize – in fact, when the cancer itself dies – it can leave fragments of altered DNA, separate from any cancer cell, in the patient’s blood or urine.
It’s this cell free (or circulating free) DNA that, Takaku said, can now be isolated and analyzed in serum samples, aiding in the early detection and more effective treatment of cancer.
According to the results of a study recently conducted by Takaku’s team, in collaboration with Dr. Mamoru Takada at Chiba University in Japan, the pre- and post-treatment analysis of the cfDNA in cancer patients’ blood can tell health professionals more accurately how various chemotherapies are working among patients with different genetic profiles.
“We profiled cell-free DNA from more than 70 breast cancer patient samples and identified clear differences between breast cancer patients and healthy donors, as well as between patients before and after treatment,” Takaku said of the paper his team published in the Nature-affiliated journal Communications Medicine. “We also observed patterns that may help distinguish between drug-resistant and drug-sensitive cases. These findings obviously have potential clinical implications.”
Such implications include providers improving the likelihood of stopping cancer by getting patients the right treatment sooner by knowing if a certain therapy is or isn’t working.
Assessing chemotherapy
Put differently, because cfDNA patterns change after treatment and differ between patients undergoing the same treatment, cfDNA appears to serve as a simple biomarker that can help providers monitor treatment efficacy, predict patient response, and support personalized cancer care.
In this case, said Takaku, the research team explored how the chemotherapy drug abemaciclib affected the cfDNA of breast cancer patients.
Known as a cyclin-dependent kinase (CDK) inhibitor, abemaciclib works by dampening the function of the kinases (CDK4/6) in the cancer cells that affect the cell division process, slowing cancer growth.
“We tried to analyze the difference between the DNA sequencing patterns before and after the treatment of this particular drug, and we saw some important changes,” Takaku smiled. “This suggests that we can use this DNA-based technique to monitor the changes happening in the cancer cells. This will affect each patient’s treatment, allowing us to see who responds well to this drug versus who doesn’t.”
Meaning, Takaku said, cfDNA could serve as the basis for a new blood test that more effectively monitors the effects and efficacy of not only abemaciclib but any number of chemotherapies.
“Researchers are desperate to have a better way to predict tumor origin and also better detection for when tumors are small,” the researcher continued. “Because when you surgically remove tumors, we want to have a way to detect the added signs of metastases or recurrence. That’s why we’re trying to develop the new method.”
From noise to signal
All of which gets us back to the notion that the body itself is a type of radio full of both noise and signal. Calling DNA a “very noisy” environment, Takaku offered that the next step in improving cancer treatment is improving the signal: clearing away the noise to truly see how cancer or the medications that kill it affect cellular function.
“Because each person has different reasons for their own genetic ‘noise,’ right?” Takaku said. “It could be a sign of infection, or maybe someone has ongoing inflammation because of their exposure to a certain viruses. Or maybe it’s just pain.”
The key is understanding the reason for cellular noise, which often affects the “signals” in question.
“Once we start isolating these individuals’ noise, it might start making more sense for us.”
To that end, Takaku concluded, his team is exploring the process of the commercialization of a host of potential products, including the use of nanotechnology in the body.
“We are actively developing a nano device to purify the DNA,” he said. Such a device, if approved, would allow the user to “wash” the DNA in a given blood sample, clearing out the noise and allowing the researcher to see cellular processes with a minimum of static.
All with a minimum of resources, which can only benefit smaller, resource-strapped health systems.
“I feel this will be very useful for rural health because if smaller hospitals don’t have fancy machines or a big laboratory, we can provide this nano device, or they just need to send couple drops of blood to us and we can purify the DNA for analysis,” Takaku said. “Our initial study used very local blood samples – patient samples coming from North and South Dakota. Establishing a strong collaboration with our local hospitals is very important for me, so that we will have access to patients. I want to help all the patients in our state and advance a way to detect the cancer better.”
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Brian James Schill
Director, Office of Alumni & Community Relations
UND School of Medicine & Health Sciences
701.777.6048 direct | 701.777.4305 office
brian.schill@UND.edu | www.UND.edu