New findings on chemotherapy resistance in breast cancer, which may lead to the development of more effective therapies, have been published by scientists from the Biomedical Center of the Slovak Academy of Sciences (BMC SAS) in the journal Drug Resistance Updates, one of the world’s most prestigious scientific journals in the field of pharmacology and pharmacy.
The article, whose first author is young researcher Lenka Trnková from the Department of Molecular Oncology at BMC SAS, shows that tumor cells acquiring resistance to the chemotherapeutic drug paclitaxel undergo extensive epigenetic changes, alongside genetic alterations. DNA methylation determines which genes are active or silenced. When this regulation is disrupted, some important genes may be switched off while others are activated. In tumor cells, this can lead to the formation of proteins that help them survive treatment.
“Research focused on DNA methylation helps reveal how and why tumor cells become resistant. A better understanding of these mechanisms can lead to early detection of treatment failure, more accurate selection of therapy for specific patients, and, in the future, the development of new treatments that could circumvent or completely prevent resistance,” explains Dr. Lenka Trnková.
Breast cancer is the most common cancer in women. More than 30,000 women in Slovakia live with this disease, and approximately 1,000 women die from it each year. One of the biggest obstacles to successful treatment is the development of resistance. In practice, this means that a therapy that was initially effective gradually stops working because tumor cells are able to adapt. This phenomenon is one of the main reasons why the disease can worsen or return.
As part of this research, the authors created a detailed molecular profile of resistant cells. They derived cell lines resistant to the chemotherapeutic drugs paclitaxel and doxorubicin and comprehensively characterized them at the level of functional changes, gene expression, mutations, changes in copy number, and DNA methylation. The authors collaborated on the research with laboratories in France, Norway, and the Czech Republic. This made it possible to develop preclinical models from tumors and verify methylation profiles in clinical samples from patients.
The journal Drug Resistance Updates publishes articles on drug resistance in infectious diseases and cancer, as well as novel drugs and treatment strategies aimed at adressing this challenge . The first author, Dr. Lenka Trnková, a large part of the research team, and the last authors of the article, Dr. Božena Smolková and Dr. Verona Buociková, are from BMC SAS.
Link to the full scientific article: https://pubmed.ncbi.nlm.nih.gov/41529624/
Text and photo: E. Rybárová, BMC SAV
Illustration: Created in BioRender.com
