Researchers study prevalence of DNA rings in cancer

Compilation
Researchers from Stanford Medical University (USA) published three scientific studies in Nature in which they report how the small circles were called cfDNA or extrachromosomal DNA, Until recently, they were considered unimportant, but they are the main cause of many types of human cancer. They detail the prevalence and prognostic impact of these circles. in almost 15,000 cases of human cancer. In addition, they highlight a new type of inheritance that overrides a fundamental law of genetics, and describe targeted cancer therapies that are already in clinical trials.

The team, known as eDyNAmic, is a group of international experts led by a pathology professor. Paul Michel. “We are in the process of completely new understanding of a common and aggressive mechanism that causes cancer. “Each paper is noteworthy individually, and together they represent an important turning point in the way we view the occurrence and progression of cancer.”

– says Paul Michel, also a researcher at the ChEM-H Sarafan Institute at Stanford Medical University. Additionally, the work also involves Howard Chang, a professor of dermatology and genetics and an investigator at the Howard Hughes Medical Institute, who co-authored two of the three papers.

Paul Michel: “We are in the process of a completely new understanding of a common and aggressive mechanism that causes cancer”

cfDNAs are circular pieces of DNA found outside the normal chromosomes inside cells. They often contain oncogenes, that is, genes that are associated with the development of cancer. Over the past few years, it has been discovered that these small DNA circles They play a critical role in the growth and persistence of cancer cells when present in large quantities. In 2017, Michel’s team showed that these cfDNAs are more common than originally thought, leading to new questions about how tumors might be more aggressive or resistant to treatment.

Three scientific studies

In the first of three studies, published in 2023, the team analyzed more than 15,000 tumor samples from 39 types of cancer. They found that 17.1% of the tumors studied contained cfDNA and that its presence was associated with worse prognoses, including a higher prevalence of metastases and shorter patient survival. In addition to oncogenes, cfDNA also contains sequences called

amplifierswhich are elements that activate other genes in the same circle, promoting tumor growth.

In the first study, they found that 17.1% of tumors contained cfDNA and that its presence was associated with a worse prognosis.

Chang emphasized that interactions between different cfDNAs are critical for disease development, representing new insights into how tumor genetics are organized. “This research we have genetic background and mutational characteristics identified “This gives us clues about how cancer starts and spreads,” explains.

The second paper by Michel and Chang examined how cfDNAs are distributed during cell division. While DNA segregation in chromosomes occurs in a more controlled manner, cfDNA segregates randomly. This allows some daughter cells to inherit multiple copies of cfDNA, increasing the likelihood that they can avoid environmental or pharmacological problems. develop drug resistance.

In a third study, they report a control protein called CHK1 that causes the death of tumor cells containing cfDNA.

A third paper, co-authored by Chang and Michel, reports that blocking the activity of an important checkpoint protein called CHK1 causes tumor cell death containing cfDNA grown in the laboratory and causing tumor regression in mice with stomach tumors caused by DNA rings. “It makes a difference for cancer cells.” warns Chang. “WITHThey are addicted to this excess transcription and cannot stop. We turn it into a vulnerability that leads to their death,” he explains.

The results were so promising that CHK1 inhibitor It is now in early-stage clinical trials in people with certain types of cancers with multiple copies of oncogenes in their cfDNA. “These papers show what can happen when researchers from different laboratories come together for a common goal,” Michelle emphasizes. “Science is a social enterprise, and together, using many ways to bring data together from many different sources, we have shown that these results are real and important. “We will continue to study the biology of cfDNA and use this knowledge to benefit patients and their families,” he states.