Researchers from Sheba and Meir Medical Center are tracking DNA and RNA from the tumor throughout treatment. In 15%–20% of patients, a signature of DNA segments was found that changed as the tumor shrank.
Researchers from Sheba Medical Center and Meir Medical Center are examining whether repeated blood tests can predict which ovarian tumors will respond well toChemotherapy Whereas tumors are expected to show resistance to treatment.
In the study, which includes about 100 patients, blood and tumor tissue samples are collected before the start of chemotherapy, during it, and on the day of surgery. The researchers look for DNA fragments in the blood andRNA originating from the tumor, as well as changes in immune system cells and other markers that indicate the destruction of the tumor or its continued development.
So far, a specific signature of segments has been found in 15%–20% of patients. Tumor DNATheir number increased after the first treatment, likely due to the destruction of tumor cells and the release of their contents into the bloodstream, and subsequently decreased as the tumor shrank.
The goal is to develop a blood test in the future that will allow doctors to understand during chemotherapy whether the treatment is working, rather than waiting until surgery to assess the response.
A disease that is often diagnosed at an advanced stage
Ovarian cancer More common after menopause, but may also occur in younger women. The most common and aggressive type is high-grade serous carcinoma, which is now believed to often begin in the cells at the tip of the fallopian tube.
The disease can spread from the fallopian tube or ovary to other organs in the reproductive system and the abdominal cavity. When diagnosed early, the chances of survival are high, but only a minority of patients are diagnosed when the tumor is still confined to the area where it started.
One of the risk factors for ovarian cancer and breast cancer is carrying gene mutations. BRCA1 and-BRCA2Certain founder mutations in these genes are relatively common among Jews of Ashkenazi descent, and therefore research in this field is of particular importance in Israel.
Not every tumor responds the same way.
Treatment for ovarian cancer is tailored to the stage of the disease, the patient's condition, and the possibility of surgically removing the tumor.
Some patients with advanced disease are first given chemotherapy to shrink the tumor. After several cycles of treatment, surgery is performed to remove the remaining tumor tissue, followed by chemotherapy to destroy microscopic cells that cannot be seen during surgery.
According to Dr. Lebanon Foundation, an oncologist who treats breast and ovarian cancer patients and head of the Ovarian Cancer Research Laboratory at Sheba, not all tumors respond equally to treatment.
“Currently, patients receive treatment that is largely based on a similar protocol, although it is clear that it is not equally effective for everyone,” she says. “Therefore, it is essential to understand in advance who is likely to benefit from it and who needs personalized treatment.”
According to her, examining the biological properties of the tumor after initial chemotherapy may teach which cells survived, what their resistance mechanisms are, and what additional treatment may be effective against them.
How can you predict which ovarian cancer will respond well to chemotherapy and which will not?
The current study, supported by a grant from the National Science Foundation, includes about one hundred patients with ovarian cancer treated at Sheba and Meir Medical Center.
Tumor tissue samples were taken from the patients, and blood tests were collected before, during, and after the first three cycles of chemotherapy, on the day of surgery.
The samples measured components that come from the tumor tissue. When tumor cells are destroyed, some of their contents are released into the bloodstream, including genetic material and other molecules. Changes in their amounts may indicate whether the treatment is harming the tumor.
The researchers are examining, among other things, DNA and RNA fragments originating from the tumor, as well as the number and composition of immune system cells. The number of these cells may change as a result of the destruction of tumor cells, but also as a result of the damage that chemotherapy causes to healthy cells.
All samples are submitted for analysis using molecular, biochemical, and genetic methods.
"The goal is that comparing blood tests and tumor samples at different times will teach us about the resistance mechanisms that allow the tumor to survive," says Dr. Lebanon. "This way, we may be able to predict which tumors will respond well to treatment and which will not, and fine-tune the continuation of treatment."
Genetic signature in blood
The study is still ongoing, but so far, a characteristic signature of DNA segments originating from the tumor has been found in 15%–20% of patients.
The number of fragments increased immediately after the first chemotherapy treatment. The researchers believe that the increase was caused by the tumor cells being destroyed and releasing their contents into the blood.
Later, as treatments progressed and the tumor shrank, the amount of DNA fragments decreased. When fewer tumor cells remained, the amount of genetic material released from them also decreased.
Such a pattern may allow researchers to assess, through subsequent blood tests, what the tumor will look like at the time of surgery and whether chemotherapy has caused extensive or only minimal change in it.
It is important to emphasize that the signature has only been identified in some patients so far. The study does not yet provide a test that is appropriate for every patient, and it has not yet proven that changing treatment based on the signature actually improves the chances of recovery.
Identify early treatment that is not working
In patients whose blood did not show a characteristic change in DNA segments following chemotherapy, the researchers want to learn whether this is a tumor that does not respond well to treatment.
If a consistent link is found between the absence of the signature and resistance to chemotherapy, it may be possible in the future to consider early treatment modification, rather than continuing with ineffective treatment.
The change may include a different chemotherapy drug, targeted therapy, drugs that affect DNA repair mechanisms, or other treatments, depending on the biology of the tumor. These options are not yet part of the current research, and no single treatment strategy has been determined that is appropriate for all patients.
According to Dr. Lebanon, the effectiveness of initial treatment is of particular importance.
"When the disease recurs, the chance of achieving a complete cure is greatly reduced," she says. "So if we can improve initial treatment and identify non-responders early, we can increase the number of women who achieve long-term remission and perhaps recovery."
On the road to personalized medicine
Testing for genetic material that originates from a tumor and circulates in the blood is sometimes called Liquid biopsyUnlike a standard biopsy, which requires taking tissue from the tumor, a blood test can be performed repeatedly during treatment.
This way, changes in the tumor can be monitored over time and not be satisfied with the image obtained on the day of diagnosis or during surgery.
However, the amount of genetic material a tumor secretes into the blood varies between patients and between tumor types. Sometimes it is too small to be reliably measured. Therefore, further studies are needed to determine for whom the test is effective, what its level of accuracy is, and how it should be incorporated into treatment decisions.
The current study does not change the standard treatment for ovarian cancer at this stage. Its goal is to identify markers that could in the future help doctors choose more precise treatment for each patient.
FAQ
What is a liquid biopsy?
A test of blood or other body fluid to detect genetic material, proteins, or cells that originate from a tumor. It allows the disease to be monitored without taking a new tissue sample each time.
What are tumor DNA fragments in the blood?
These are pieces of genetic material that are released into the bloodstream when tumor cells die, are destroyed, or break down.
Can the test already determine which treatment each patient will receive?
No. The study is still ongoing, and the signature has only been found in some patients so far. Further validation and follow-up are needed before clinical use.
Why are samples taken at several times?
Comparing the blood before, during, and after treatment allows us to see whether the amount of substance originating from the tumor increases following the destruction of cells and then decreases as the tumor shrinks.
Do all ovarian cancer patients receive chemotherapy before surgery?
No. The decision whether to start with surgery or chemotherapy depends on the stage of the disease, the extent of the tumor, the patient's condition, and the chance of removing the disease with surgery.
Does a BRCA mutation necessarily cause cancer?
No. Being a carrier increases the risk of breast and ovarian cancer, but does not guarantee that the disease will develop.
More on the subject on the science website
- A gene has been discovered that helps in understanding ovarian cancer
- A new biomarker may improve the treatment of lung cancer patients
- The fungi that hide inside cancerous tumors
- The new players in the war on cancer
- How mRNA and DNA vaccines could soon treat cancer, HIV, autoimmune disorders, and genetic diseases
