Earlier cancer detection: UCSC researchers working on promising ‘liquid biopsy’

Scientists work in the Daniel Kim Lab, which focuses on stem cells and cancer research at UC Santa Cruz, in 2019.
Scientists work in the Daniel Kim Lab, which focuses on stem cells and cancer research at UC Santa Cruz, in 2019.
(Carolyn Lagattuta / Via UCSC)

Could this research, produced by Daniel Kim’s UC Santa Cruz lab of eight, lead to earlier detection and treatment for cancer, which kills more than half a million Americans a year?

Early detection is a big key in stopping cancer, but doctors have long had inadequate tools to find the disease early enough to treat it well.

A Q&A with UCSC assistant professor Daniel Kim

Now, Daniel Kim, an assistant professor of biomolecular engineering at UC Santa Cruz, has co-led research that could lead to a simple diagnostic tool that can detect cancer — the second-leading cause of death in the United States after heart disease — in its preventable stages.

A study published last month by Kim and several students at the Daniel Kim Lab shows that they might be on track.

The researchers believe they found a molecule that can lead to such a new tool.

That molecule, RNA (ribonucleic acid), has been mostly known for being a “messenger” because it converts the genetic instructions from DNA (deoxyribonucleic acid) and changes it into protein. However, scientists have shown in recent genomic studies that the majority of RNA doesn’t make protein and is “noncoding.”

Further, certain types of RNAs are released when the mutated KRAS gene, which is thought to lead to cancer formation, is present. The KRAS gene manages the RNA produced in a cell.

“The reason most patients die from cancer is because it’s detected too late, and it’s spread to other parts of the body,” said Kim. “But if you could detect cancer before it had a chance to spread to other parts of the body, then you could potentially treat the patient more effectively with different therapies or with surgery, and potentially even cure the patient.”

While almost 600,000 Americans died from cancer in 2019 — the most recent year for available data — the annual rate of cancer deaths in the U.S. has gone down every year since 2015.

However, as people paused many elective procedures and screenings decreased amid the COVID-19 pandemic, there is concern that cancers that could have been detected during the early preventable stages might have been missed, leading to a higher number of delayed diagnoses.

Detection includes a spectrum of screening methods including imaging radiology tests, endoscopy procedures and biopsy tests.

Kim launched his lab about six years ago, when he came to UCSC from Pasadena-based Caltech, where he served as a fellow in the Division of Biology and Biological Engineering. When he’s teaching, Kim instructs both graduate and undergraduate courses, including ones in precision medicine and computational biology.

At his lab, he and a team of eight students focus on noncoding RNA, specifically to understand how cancer starts and to find new biomarkers for detecting cancer early. The team started working on this recent study several years ago and will continue to develop the technology for a liquid biopsy. A Ph.D. candidate in Kim’s lab, Roman Reggiardo, served as the lead author of the study.

In addition to his lab work, Kim is affiliated with UCSC organizations including the UC Santa Cruz Genomics Institute, the Institute for the Biology of Stem Cells and the Center for Molecular Biology of RNA, and he’s an associate member of the Canary Center at Stanford for Cancer Early Detection.

This interview has been edited for clarity.

Lookout: Can you describe the main findings of the study?

Daniel Kim: At the very earliest stages of cancer, these RNAs, called non-coding RNAs, respond to this very early mutation that occurs in cancer, this mutation in this gene called KRAS. We identified how this early mutation changes this non-coding RNA landscape within a cancer cell. What was really interesting is that these RNAs don’t just stay within the cell, they’re actually secreted from the cell in these little packages, or vesicles. We can identify those RNAs that are being released by these cancer cells. We believe that these RNAs, these non-coding RNAs that are being released at this very early stage of cancer, can be used as biomarkers to detect the earliest stages of cancer.

I think we are probably the first to show that this mutation in KRAS affects the non-coding RNA landscape, and also to identify which of those RNAs are released by the cell. Other people have studied the gene KRAS as it’s a pretty famous cancer gene, but they primarily focused on how this mutation affects protein coding genes. The novelty of our work is that we’ve identified how this gene affects non-coding genes that don’t make proteins, these non-coding RNAs.

An international team of scientists, co-led by UCSC Genomics Institute Associate Director Karen Miga, completed the...

Lookout: Tell us more about the liquid biopsy the team is developing and how long will this take to develop.

Kim: Liquid biopsies are where you can take blood from a patient, and you can detect the signal that’s coming from the cancer, whether that’s RNA or DNA or proteins. We are kind of taking this RNA signal, and we’re looking for [the signal] in the blood of cancer patients. We believe that this will allow patients to be diagnosed noninvasively just with a blood draw, simply by identifying the RNAs that are being released by the cancer cells within the body. That’s ongoing work right now to follow up on the study to develop this RNA liquid biopsy.

It takes a few years; I can’t say definitively how long the timeline will be. But it is more challenging to do this kind of research when we don’t have a medical center, because we don’t have access to patient samples, to patient data. That definitely slows things down a little bit. But in terms of just developing the technology, we’re confident we can do in the next few years.

Lookout: Why is this research important?

Kim: There are companies that are developing these types of diagnostic tests for cancer early detection, but they have been focusing primarily on DNA. What at least some studies have shown is that DNA just doesn’t work well for detecting cancer in the earliest stages, probably because there’s just not enough DNA circulating in the blood that’s being released by cancer cells at the earliest stages. But for RNA, it’s just continuously released by cancer cells, even at early stages. That’s why we’ve been focusing on RNA to be able to detect cancer at the earliest stages. This is such an urgent need, given that millions of people around the world do die from cancer every year. The sooner we can get this technology into the clinic, hopefully the more lives we’ll be able to save. We definitely have that sense of urgency to be able to provide better options for diagnosing cancer early. That’s where we hope our technology that we’re developing will enable the patients to find out sooner, when they can receive potentially curative treatments.

Also, the value in this technology that we’re developing is that it’s not restricted to just cancer; it could enable the diagnosis of other types of diseases as well — whether it’s a neurodegenerative disease. We’re also studying COVID right now, to better understand how COVID affects the body. There are a lot of different applications that we have envisioned for this RNA and liquid biopsy technology beyond cancer diagnosis. It’s really a broad, potential diagnostic test. All of the organs in our body, all the cells in our different organ systems, they release RNA in the blood. We’re able to get a snapshot of the health of every organ system in the body using this tool, so this could be beneficial for understanding many different types of diseases.

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