Researchers identify how the most common breast cancer becomes resistant to treatment


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

City of Hope, a world-renowned cancer research and treatment center, has identified how cancer cells change in early-stage breast cancer patients and become resistant to hormone or combination therapies, according to a new study published a Nature’s cancer.

About 80% of cancer cases are hormone-positive receptors, that is, these they need estrogen or progesterone to grow, according to the American Cancer Society. Doctors currently treat people with estrogen receptor-positive (ER +) breast cancer which inhibits estrogen levels and cell cycle activity. Although these therapies usually reduce tumors initially, approximately 90% of metastatic patients and 50% of stages 2 and 3 develop resistance.

A research team led by Andrea Bild, Ph.D., a professor in the Department of Research in Medical and Therapeutic Oncology at City of Hope, used monocellular RNA sequencing to identify resistant traits that cells acquire. carcinogenic cells; these cancer cells may persist despite therapy. The team also identified when these resistant traits are acquired and found them as early as two weeks after starting a treatment regimen, which is months faster than current methods used to measure response to treatment.

“Yes they are able to identify the development of tumor resistance sooner, then they can quickly change speed and offer a different treatment regimen that could eventually lead to the remission of the breast cancer patient instead of continuing down a path that may not achieve a positive result “, Bild” With the current set of precision medicine tools available, medical professionals could measure the patient’s response to treatment earlier to offer treatment options that are more likely to work for each patient. “

Bild and colleagues studied the evolution of DNA and RNA in breast tumor cells of postmenopausal women with ER + breast cancer who were enrolled in the FELINE trial. These patients were treated with endocrine therapy (letrozole) alone and in combination with cyclin-dependent kinase inhibitor (CDK) therapy (ribocyclib), a treatment that prevents the growth of tumor cells. Patients were treated with targeted therapy in a neoadjuvant setting, i.e., before surgery to remove the tumor, to assess the response. Tumor biopsies from more than 40 patients were processed and analyzed from cells taken earlier, two weeks later, and six months from the start of endocrine and combined treatments.

City of Hope researchers found that resistant cells that persist even after endocrine cell cycle inhibition therapy (CDK4 / 6) tend to change their growth engine. use estrogen signaling to use alternative growth factor receptors and re-establish cell cycle pathways. For example, resistant cells avoid blocked pathways by activating alternative signaling pathways such as growth receptors and MAPK signaling; this rewiring allows cancer cells to continue to grow despite inhibitors of cell cycle drugs and estrogen. Targeting these acquired pathways of resistance with appropriate therapies can help physicians in the future treat patients with early-stage ER + resistant breast cancer.

“The study is impressive in its scope as it presents a complete genomic profile of the longitudinal samples from several patients,” said Suwon Kim, Ph.D., who was not involved in the research and is an associate professor at the ‘Translational Genomics Research Institute (TGen)), affiliated with City of Hope and faculty member at the University of Arizona College of Medicine. “The results are significant, revealing the emergence of specific alternative pathways in individual tumor cells as they become resistant to CDK inhibitors and endocrine therapy. The results of the study offer opportunities for guided therapy intervention. evidence of therapy-resistant breast cancer “.

Understanding how tumor cells change and rapidly change signaling pathways so that they can persist after combined neoadjuvant cancer treatment will allow scientists to design new treatment regimens aimed at tumor resistance. Bild and colleagues are now identifying drugs that block traits found specifically in cancer-resistant .

“Early-stage breast cancer ER + and PR + (positive progesterone receptor) can often be cured and we must continue in this line of research to design therapy strategies that provide a positive outcome for the patient to last,” he said. Bild. “I recommend that doctors continue to collect when possible biopsies to be able to measure cellular responses during treatment to understand how the patient’s tumors respond. In addition, we need to look at RNA changes and not just DNA modifications, as these changes can more generally capture the mechanisms of resistance. “

He added: “I am grateful to patients participating in clinical trials so that scientists can continue to find better ways to treat this disease.”

Orientation against estrogen-resistant breast cancer

More information:
Jason I. Griffiths et al, Monocellular cell genomics reveals a convergent subclonal evolution of resistance as early-stage breast cancer patients progress into more CDK4 / 6 endocrine therapy, Nature’s cancer (2021). DOI: 10.1038 / s43018-021-00215-7

Citation: Researchers identify how most common breast cancer becomes resistant to treatment (2021, June 24) recovered on June 24, 2021 at -resistant-treatment.html

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