Changes in tumor DNA help predict cancer’s next move

Knowing whether a tumor can grow or spread to other parts of a patient’s body can be key to survival.And now scientists are one step closer to unlocking the ability to predict it

In a series of seven papers published today (Wednesday, April 12) Nature and natural medicineUK-funded researchers based at the Francis Crick Institute for Cancer Research and University College London (UCL) predict how changes in cancer cells’ DNA predict their future behavior. It explains how it can be done.

This includes where and when cancer spreads to other parts of the body in a process known as metastasis, which is responsible for most cancer deaths worldwide.

The discovery could one day allow doctors to use blood tests to predict how a patient’s cancer will grow and spread, allowing real-time tracking and rapid adaptation of treatment. will be It also provides a potential route by which clinicians can analyze the risk of disease recurrence after surgery.

The study was conducted on lung cancer patients, but the scientists say the findings can also be applied to other types of cancer, such as skin cancer and kidney cancer.

These studies are the culmination of nine years of research from Cancer Research UK’s £14 million TRACERx study and the first long-term study of how lung cancer evolves. TRACERx is a national research effort involving more than 800 of his patients in clinical trials and his community of 250 researchers based in 13 hospitals across the UK.

The principal investigator, based at the Francis Crick Institute in London, UCL, and Professor Charles Swanton, Chief Clinician at Cancer Research UK, said:

“TRACERx recognizes that cancer is not static and neither should the way patients are treated.”

“What makes the TRACERx project particularly powerful is treating the tumor as an ever-changing ‘ecosystem’ of diverse cancer cell populations.

“By looking at the whole tumor, we can see how these populations of cells interact and even compete with each other. It also allows us to observe how tumors develop, spread and respond to treatment over time, giving hope to millions of patients in the future. can do.”

In these seven studies, Crick and UCL researchers followed 421 of the 842 TRACERx participants from the time of diagnosis to monitor how their tumors changed over time. The patient had non-small cell lung cancer (NSCLC), the most common type of lung cancer.

Among the key findings of the seven papers, the researchers found:

• Tumors can be made up of different cancer cell populations that carry an ever-changing set of genes. The more diverse these tumors are, the more likely it is that a patient’s cancer will recur within a year of treatment.
• Some patterns of DNA changes when observed in a patient’s tumor indicate what that patient’s cancer may do next.
• These patterns can show doctors which parts of the tumor may grow and spread to other parts of the body in the future.
• Blood tests can be used to monitor these changes in tumor DNA in real time, helping doctors spot early signs that the cancer is coming back or not responding to treatment.

Constant changes to cells enable tumor growth

Tumors are made up of different ‘populations’ of cancer cells, all with different genetic mutations. The more diverse these mutations are, the more likely the tumor is to evolve and acquire resistance to therapy.

Researchers found that specific patterns of genetic mutations in cell populations caused cancer to recur earlier in patients, within a year after surgery.

The pattern of these mutations also indicates whether the tumor is likely to spread beyond the lungs and chest to other areas of the body.

Armed with this information, doctors will one day be able to predict whether patients with early-stage cancer who could be successfully treated with surgery will eventually see their cancer come back.

In another discovery, researchers found that the genetic diversity of cell populations within tumors is due not only to genetic changes, but also to the way genes are expressed.

Changes in gene expression can influence important aspects of cancer biology, such as whether tumors recur after surgery.

In this case, researchers suggest that a doctor perform the treatment. lung cancer patient By identifying people at highest risk of their cancer coming back after surgery and following up with further treatment, we can intervene early and prevent the cancer from coming back.

Identify what causes cancer to spread

The researchers also took a closer look at how lung cancer spreads in TRACERx participants.

They identified which cells within the tumor were most likely responsible for future cancer spread (metastasis). These cells are likely to have certain changes in their genes. These indicate that cells are likely to leave the tumor and migrate to other parts of the body where they may grow into a new tumor.

Since the majority of cancer deaths are due to metastasis, understanding which parts of the tumor trigger this process will help researchers target treatments specifically to prevent the spread of cancer. can be targeted.

Changing the way people track cancer

TRACERx scientists also investigated whether tumor changes and their genetic diversity signatures could be tracked without the need for surgery or biopsy. This is a type of invasive medical procedure in which a small sample of tissue is taken and tested in a laboratory.

By analyzing DNA released into the bloodstream from tumor cells known as circulating tumor DNA (ctDNA), the presence of ctDNA in the blood before and after surgery suggests that the patient’s cancer is highly likely to recur in the future. I found that it suggests

The presence of tumor DNA in the blood is not the only indicator that cancer may spread or come back. Researchers have found that the microscopic patterns created by the arrangement of tumor cells are associated with the risk of cancer recurrence.

A blood test that reads ctDNA could allow doctors to track someone’s cancer in real time and customize treatment for that patient.

Currently, the best option for monitoring a patient’s tumor is a biopsy or tissue extraction during surgery. Both are invasive and time-consuming options that provide a definitive snapshot of tumor behavior at specific time points.

Analysis of ctDNA uses a minimally invasive blood test to provide a complete picture of how tumors are changing over the course of a patient’s disease. This allows doctors to treat people more aggressively and quickly change ineffective treatment plans. ”

Dr Ian Fawkes, Executive Director of Research, Cancer Research UK

TRACERx is already in its next phase, known as TRACERx EVO, with nearly £15m in additional funding over the next seven years to advance our understanding of tumor evolution and use that knowledge to treat cancer patients. We are going to change the way we do things.