Ovarian cancer is the fifth leading cause of cancer death in women, and part of its frustrating stubbornness to treatment and high rate of recurrence may be due to amazing cellular cooperation.
New research has revealed how chemotherapy-resistant quiescent cells behave during and after treatment, and how they directly affect surrounding cancer cells.
Chemotherapy primarily targets rapidly dividing cancer cells, making treatment of slow-dividing quiescent cells difficult. Researchers at the University of Pittsburgh and the University of Pittsburgh Medical Center Hospital found that not only dormant cells resist aggressive drug intervention, but they also secrete a protein known as follistatin that slows the rate of division of neighboring cells, causing them to I’ve seen it become more tolerant.
Dr. Ronald Buckanovich, Pitt Professor of Medicine, Co-Director of the Center for Women’s Cancer Research and co-author of the paper, said: study. “In response to chemotherapy, dormant cells secrete follistatin, which acts like a protective signal throughout the flower.
“When chemotherapy is stopped, follistatin levels drop and the cells start growing again. It’s like a barometer of ‘fitness to grow,'” he added. “This may explain why ovarian cancer often comes back so quickly.”
The team found that in both mice and laboratory-grown human cells, quiescent cells stimulated the production of follistatin in response to chemotherapy drugs. When researchers blocked secretion of this protein, it lost its shielding effect on surrounding cells, making them vulnerable to chemotherapy again. .
“It was thought that quiescent cells produce factors that resist chemotherapy, but the fact that they protect their neighbors and amplify chemoresistance was surprising,” said Dr. Buckanovich. rice field. “When these neighbors learn to quiesce themselves, which protects them, more and more resistant cells will persist, leading to cancer recurrence.”
The American Cancer Society estimates that about 20,000 women will be diagnosed with ovarian cancer in 2023. Surgery and chemotherapy are effective, especially in the early stages, but more than 70% of her patients treated for this disease have cancer recurrence, which is rare at this time. Heal.
“If we can reverse chemoresistance and reduce patient relapses, we may be able to increase cure rates,” Dr. Buckanovich said. “Even if this approach worked for her 20% of patients, it would be a staggering amount, as about 14,000 patients die from ovarian cancer each year.”
The team also compared samples of ovarian cancer patients before and after chemotherapy and found that follistatin levels doubled or tripled immediately after treatment. We believe that this may lead to follistatin suppression therapy for
Follistatin has previously been associated with improved outcomes in lung cancer patients receiving chemotherapy.
“For me, the most exciting part of this study is the fact that we saw an amazing patient response to chemotherapy within 24 hours,” Buckanovich said. “These data reinforce our findings in mice and suggest that follistatin is a novel target for improving ovarian cancer response to chemotherapy.”
The study was published in a journal clinical cancer research.
Source: University of Pittsburgh
