As cancer diagnostics continue to evolve, the ability to detect and treat the disease at an early stage is improving significantly. One of the recent groundbreaking innovations is liquid biopsy – a method that detects genetic mutations without invasive procedures. Alongside this, genetic and epigenetic research is increasingly critical in advancing cancer diagnostics and treatment.
"When the concept of liquid biopsy was still emerging, I applied for a postdoctoral fellowship under the Marie Skłodowska-Curie Actions program. My application was rejected with the argument that if such a method were possible, cancer would have already been cured. That only motivated me to dive even deeper into this field – and today, we are witnessing its real impact," says Prof. Sonata Jarmalaitė from the Vilnius University Life Sciences Center.
Vilnius University Scientists - Pioneers in Liquid Biopsy
Prof. Jarmalaitė's research group is best known for its work on liquid biopsy, which allows for detecting tumor-related genetic alterations not in the tumor itself but in bodily fluids circulating throughout the body.
"As blood and other bodily fluids pass through a tumor, they collect nucleic acids from dead cancer cells. Tumor DNA can be detected in saliva, urine, and other body fluids, making it a valuable diagnostic tool. We were among the first in the world to identify cancer DNA in urine, which is why we truly consider ourselves pioneers of liquid biopsy in Lithuania," explains Prof. Jarmalaitė.
Dr. Rasa Sabaliauskaitė from the National Cancer Institute adds that their research focuses on detecting circulating nucleic acids in urine. These markers are linked not only to prostate and bladder cancer but also to breast cancer detection efforts.
"Our group specializes in minimally invasive cancer diagnostics. Urine, being a non-invasive sample, is highly suitable for research. As we know, cancer patients often have fragile blood vessels, making blood collection challenging. Liquid biopsy offers a solution by enabling disease monitoring even after tumor removal."
A Breakthrough in Cancer Monitoring and Personalized Medicine
Liquid biopsy is already used in clinical settings and has become a standard component of lung cancer diagnostic protocols.
"We often joke that introducing liquid biopsy at the National Cancer Institute took neither too long nor too short – 25 years of technological development, but once we had the necessary expertise, specialists, and scientific research, it was implemented within two weeks," adds Dr. Sabaliauskaitė.
Genetic diagnostics laboratories play an essential role in major oncology clinics in Lithuania and worldwide.
"Diagnosing hereditary cancer is impossible without genetic testing. Without precise genetic screening, targeted therapies and modern cancer treatments cannot be prescribed," notes Prof. Jarmalaitė.
According to her, DNA sequencing, once purely a research tool, has become a routine procedure in cancer diagnostics.
"Today, a hereditary cancer diagnosis is not confirmed without DNA sequencing. For precision medicine treatments, an accurate genetic diagnosis is crucial. Physicians must know exactly what genetic alteration is present to prescribe the appropriate therapy. This technology is already widely used in clinical practice, and as its application expands, patients will benefit significantly. The effectiveness of targeted therapies is much higher, and survival rates are improving rapidly," she explains.
While liquid biopsy is not yet widely used due to its complexity, its role in precision medicine is expected to grow.
"In the future, doctors will need to prescribe specific treatments at the right time and in the correct dosage – something that cannot be done without medical geneticists. Currently, we monitor cancer progression through blood-based liquid biopsies, but eventually, urine-based biopsies will take their place, offering a much simpler approach," adds Dr. Sabaliauskaitė.
Epigenetic Markers as a Non-Invasive Alternative
In addition to genetic research, epigenetic studies are also being actively developed in collaboration with clinicians.
"We have been searching for epigenetic markers specific to kidney cancer that could be used for early diagnosis. Our research has identified a unique set of epigenetic markers that could be tested using liquid biopsy samples – specifically urine. This is particularly relevant for early-stage kidney cancer, where some tumors progress slowly and may not require immediate treatment, only monitoring. By testing cancer markers in liquid biopsies, we aim to track these changes more precisely," says Prof. Jarmalaitė.
The incidence of kidney cancer is increasing, and the disease often remains asymptomatic until it reaches an advanced stage. Early detection is crucial, and ultrasound and radiological tests are helping to identify tumors earlier than before.
"There is a pressing need for early detection markers, as kidney biopsy is a highly complex procedure. Through collaboration with clinicians, we hope to develop a diagnostic tool useful for early kidney cancer detection. The biggest challenge remains determining when a tumor is growing and requires intervention. Our genetic and epigenetic markers provide more precise insights than ultrasound or MRI scans," Prof. Jarmalaitė explains.
Uncovering the Hidden Causes of Cancer: The Cancer Mutographs Project
Prof. Jarmalaitė and Dr. Sabaliauskaitė were part of the Grand Challenge Award-funded Cancer Mutographs project in the UK, which aimed to investigate regional and global differences in cancer incidence.
"We know the causes of many cancers, yet there are still striking variations in cancer rates across different countries and regions. Even with known risk factors such as smoking, alcohol consumption, and air pollution, there are hidden causes we have yet to uncover," says Prof. Jarmalaitė.
Lithuania was included in the study due to its high incidence of kidney cancer.
"Together with clinicians, we prepared kidney cancer biopsy samples that were sent to the Wellcome Sanger Institute in the UK. The tumors were sequenced there, and algorithms were used to identify mutation patterns linked to carcinogen exposure. In the case of kidney cancer, a unique mutation profile was found – one that does not correlate with smoking or alcohol consumption. This profile is most prevalent in the Baltic States and Poland, but the exact carcinogen remains unidentified," explains Prof. Jarmalaitė.
A decade ago, the Sanger Institute discovered that kidney failure and kidney cancer in the Czech Republic and the Balkans were caused by aristolochic acid, a compound found in traditional herbal remedies.
"Plants produce chemical defenses to survive, some of which can be carcinogenic. Whether our newly discovered mutation profile is linked to a similar plant-derived substance remains to be seen. While the medicinal plants used in our region seem harmless, further research is needed," says Prof. Jarmalaitė.
Aiming to Identify the Carcinogen and Reduce Cancer Rates
The research team is now participating in the Prominent Project, another UK-based initiative to identify pre-cancerous mutation profiles.
"Using existing data, we analyze these mutation profiles to determine their causes. Currently, these studies are conducted in laboratories. Still, once the lab findings are confirmed, epidemiological studies will follow to investigate whether certain carcinogenic substances are more prevalent in specific countries," Prof. Jarmalaitė explains.
Understanding the causes of cancer can lead to effective prevention strategies. The successes in liver and cervical cancer prevention serve as examples.
"The International Agency for Research on Cancer identified aflatoxins – mold toxins in poorly stored food – as a cause of liver cancer, leading to prevention efforts in Africa. Similarly, linking HPV infection to cervical cancer enabled the development of vaccines, dramatically reducing cases. We hope our research will also contribute to cancer prevention in the future," says Prof. Jarmalaitė.
Dr. Sabaliauskaitė emphasizes that genetic and epigenetic research is a collaborative effort involving scientists and clinicians worldwide.
"This is not a single person's discovery but a collective scientific effort to prove that a specific carcinogen causes cancer. It requires time, dedication, and teamwork. Clinicians play a key role by providing high-quality tumor samples, ensuring that scientific advancements translate into real-world clinical applications. We are also grateful to the patients who participate in these studies," she concludes.
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