Researchers identify how the most common breast cancers become refractory to treatment

A mammogram showing a normal breast (left) and a breast with cancer (right).Credit: public domain

The City of Hope, a world-renowned cancer research and treatment center, has identified how cancer cells in patients with early-stage breast cancer change and become resistant to hormone or combination therapy. Nature Cancer..

About 80% of milk Cancer cases are hormone receptor positive, which is cancer cell According to the American Cancer Society, it requires estrogen or progesterone to grow.Doctors now have people with estrogen receptor positive (ER +) breast cancer Treatment It inhibits both estrogen levels and cell cycle activity. These treatments often shrink the tumor initially, but about 90% of metastatic patients and 50% of stages 2 and 3 Breast cancer patients Develop a resistor.

Andrea Bild, Ph.D., Professor of Oncology and Therapeutics, City of Hope. The research team, led by, used a single-cell RNA sequence to identify the resistance traits acquired by cancer cells. These cancer cells can survive despite treatment. The team also identified when these resistance traits were acquired and discovered them as early as two weeks after the start of the treatment regimen. This is months faster than the current methods used to measure therapeutic response.

“if Health care provider If the onset of tumor resistance can be identified early, it is possible to switch gears quickly and ultimately relieve breast cancer patients rather than continuing a pathway that may not achieve positive results. We can offer another treatment regimen that we can, “says Bild. “With the set of precision medicine tools currently available, healthcare professionals can measure a patient’s response to treatment early and provide treatment options that are likely to work for each individual patient.”

Bild and her colleagues studied the evolution of DNA and RNA in breast tumor cells of postmenopausal women with ER + breast cancer enrolled in the FELINE trial. These patients were treated with endocrine therapy (letrozole) alone and in combination with cyclin-dependent kinase (CDK) inhibitor therapy (ribociclib), a treatment that suppresses the growth of tumor cells. Patients were treated with targeted therapy in a neoadjuvant setting, meaning prior to surgery to remove the tumor, to assess response. Biopsies from tumors in more than 40 patients were processed and analyzed from cells collected before the start of endocrine and combination therapy, 2 weeks after the start, and 6 months after the start.

Researchers at the City of Hope found that resistant cells that persist after endocrine and cell cycle (CDK4 / 6) inhibition therapy use alternative growth factor receptors and rewire cell cycle pathways from the use of estrogen signaling to the growth engine. I found that I tend to shift to. For example, resistant cells bypass blocked pathways by turning on alternative signaling pathways such as growth receptors and MAPK signaling. This rewiring allows cancer cells to continue to grow despite estrogen and cell cycle drug inhibitors. Targeting these acquired resistance pathways with appropriate treatment may help physicians treat patients with resistant ER + early-stage breast cancer in the future.

“This study is impressive in that it presents comprehensive genomic profiling of longitudinal samples from multiple patients,” said an associate professor at the Translational Genomics Institute (TGen), who was not involved in the study. One Dr. Suwon Kim said. ), An affiliate of the City of Hope, and a faculty member at the University of Arizona School of Medicine. “Results are important and reveal the emergence of alternative specific pathways in single tumor cells that become resistant to CDK inhibitors and endocrine therapy. Studies show evidence-based treatment for refractory breast cancer. It provides an opportunity for intervention. “

Scientists target tumor resistance by understanding how tumor cells change rapidly and rewire signaling pathways so that they can persist after concomitant treatment with neoadjuvant cancer. You can design a new treatment regimen.Built and colleagues are currently identifying drugs that block the properties found in cancers that are particularly resistant. cell..

“Early-stage ER + and PR + (progesterone receptor-positive) breast cancers often cure, and this series of studies needs to be continued to design treatment strategies that provide sustained positive patient outcomes. “Bild said. “If possible, we recommend that the clinician continue to collect. tumor Biopsy so that it can be measured cancer Cellular response during treatment to understand how a patient’s tumor is reacting. Furthermore, it is necessary to pay attention not only to the modification of DNA but also to the change of RNA. These changes may have a broader view of the resistance mechanism. “

“Thanks to the patients participating in the clinical trials so that scientists can continue to find better ways to treat the disease,” she added.

Targeting drug-resistant breast cancer with estrogen

For more information:
Jason I. Griffiths et al, Serial Single Sergenomics, reveals convergent subclonal evolution of resistance as patients with early-stage breast cancer progress with endocrine therapy and CDK4 / 6 therapy. Nature Cancer (2021). DOI: 10.1038 / s43018-021-00215-7

Quote: Researchers have learned how the most common breast cancers obtained on June 24, 2021 from https: // Identify if you will become resistant to treatment (June 24, 2021)

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Researchers identify how the most common breast cancers become refractory to treatment

Source link Researchers identify how the most common breast cancers become refractory to treatment

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