Health
Study reveals why some ovarian cancer patients become treatment resistant
An international team of researchers led by an Australian scientist has discovered why some ovarian cancer patients resist treatment.
Key Point:
- Researchers analyzed late-stage ovarian cancer tumors to see how they evolved to resist drug treatment
- They identified nine different resistance mechanisms and found that one of them caused resistance in almost half of the patients.
- Scientists say the discovery could help pave the way for new techniques to treat deadly cancer
The world’s first study of Published today in Nature Geneticsresearchers analyzed autopsy samples from recently deceased ovarian cancer patients to see how their tumors evolved to avoid drug therapy.
Elizabeth Christie, lead author and treatment-resistant specialist at Peter MacCallum Cancer Center in Melbourne, found that among women with high-grade serous carcinoma, the most common type of ovarian cancer, 70 to 80 % said they would become refractory to treatment over time.
“Ovarian cancer is usually very sensitive to initial treatment, but unfortunately many women relapse,” said Dr. Christie.
“At that point, the cancer may become resistant, making it more difficult to treat.”
About 1,800 women in Australia are diagnosed with ovarian cancer each year.
Most cases are diagnosed in the advanced stages of widespread disease and are associated with relatively poor overall survival.
There are no early detection tests for ovarian cancer or symptoms. bloating, difficulty eating or feeling full, frequent or urgent urination, pain in the back, abdomen, or pelvis — Early stages of cancer are often overlooked or misdiagnosed.
Dr. Christie said a better understanding of how cancer cells develop resistance to therapy could pave the way for new techniques to treat deadly cancers.
“By clarifying the processes that drive ovarian cancer resistance to therapy, we can focus on targeting these resistance mechanisms early and finding new therapies that improve patient outcomes.”
Multiple resistance mechanisms identified
Using a combination of genomic sequencing, targeted DNA sequencing, and information about immune cells and proteins, Dr. Christie and her colleagues analyzed approximately 400 tumor samples from 15 patients.
“These women donated their bodies to science after they died,” Dr. Christie said.
All patients were diagnosed with high-grade serous ovarian cancer with BRCA1/2 gene mutations and all consented to an autopsy immediately after death.
“We focused on patients with BRCA1/2 mutations because they are more common in ovarian cancer than in other cancer types, and these patients often develop resistance to treatment.” Dr. Christie said.
By studying the samples, the researchers identified nine different mechanisms that caused ovarian cancer cells to resist treatment, with one specific mechanism leading to resistance in nearly half of the patients. .
“We also found that in many patients, the cancer has developed multiple mechanisms to resist treatment.”
Despite the small number of patients involved in the study, Dr. Christie said the study provided valuable insight into the evolution of terminal disease and resistance in response to treatment.
“It is difficult to generalize [the findings] But as cancer became more resistant, it made me realize how complex the disease could be,” she said.
“Resistance occurs on many levels. It’s not just DNA, it’s RNA and protein.”
pave the way for better care
Recently, drugs known as PARP inhibitors have been successfully used to treat some women with advanced ovarian cancer caused by defects in the BRCA gene.
PARP is a protein that plays an important role in DNA damage repair. As a cancer treatment, PARP inhibitors block the protein’s activity. In other words, cancer cells cannot repair themselves and die.
However, patients whose cancer has recurred may develop resistance to these drugs, says cancer epidemiologist Penny Webb.
“They work really well until you stop working.”
Professor Webb, who heads the gynecologic cancer group at the QIMR Berghofer Medical Research Institute in Queensland, said the study, in which she was not involved, could help address the limitations of PARP inhibitors and other treatments. said there is.
“The more we know why they stopped working, the more likely we are to fix that problem,” she said.
“[The researchers] Even within a single woman, we found that so much was going on that there was no single consistent mechanism to explain why cancer became resistant.
“It suggests that if we can stop the emergence of resistance in the first place, we will have better results, because once resistance emerges, treatment becomes complicated. There is probably no single solution. .”
Dr. Christie says the findings will not only help scientists rethink how current drug therapies are delivered, but also contribute to the development of new treatments.
“In an ideal world, we would use existing treatments, but for some patients we would consider new combinations or administer them at different times, including early in the disease.
“But we also think we need to prevent resistance or start looking at new drugs that are more effective when resistance develops.”
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Sources 2/ https://www.abc.net.au/news/health/2023-02-28/ovarian-cancer-treatment-resistant-genetics-therapeutics/102026434 The mention sources can contact us to remove/changing this article |
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