The study investigates a potential new therapeutic approach for the treatment of triple-negative breast cancer

The study investigates a potential new therapeutic approach for the treatment of triple-negative breast cancer

Researchers are exploring a potential new therapeutic approach for treating triple-negative breast cancer. Amir Abdo Alsharabasy, a CÚRAM doctoral student working in Professor Abhay Pandit's laboratory, is working on developing nitric oxide scavengers to create a new treatment approach for this aggressive form of breast cancer.

Triple-negative breast cancer is invasive breast cancer that does not respond to hormone therapy drugs or the current medications that target the HER2 protein. Triple-negative breast cancer tends to be more aggressive, more difficult to treat, and more likely to recur than cancers that are hormone receptor positive or HER2 positive.

Nitric oxide is one of the most prominent free radicals produced by tumor tissue. At certain concentrations, it plays a significant role in the progression of breast cancer by causing the cancer cells to spread to other parts of the body. “Our goal is to develop injectable hydrogel formulations that can reduce or “scavenge” levels of nitric oxide while improving the production of carbon monoxide, potentially allowing us to develop a new treatment approach for triple-negative breast cancer.”

Amir Abdo Alsharabasy, a CÚRAM doctoral student

Nitric oxide interacts with various components of the large network of proteins and other molecules that surround, support, and structure tumor cells and tissues in the body. Hyaluronic acid is one of the main components of this network and the material of choice for producing these hydrogels.

“HA plays multiple roles in tumor tissue,” says Amir. "However, its interactions with nitric oxide have not been thoroughly studied. The recent study published in Biomacromolecules seeks to understand the mechanism of these interactions and the differential effects on nitric oxide levels and breast cancer cell migration."

The study is supervised by Prof. Abhay Pandit, scientific director of CÚRAM, and was carried out together with collaborators Dr. Sharon Glynn from the Lambe Institute for Translational Research and Dr. Pau Farras from the School of Biological and Chemical Sciences in the Ryan Institute at the National University of Ireland Galway,

The work examined the ability of HA to scavenge nitric oxide. The team found that the conversion of nitric oxide into certain nitrogen-centered free radicals causes the breakdown of HA, which further inhibits nitric oxide-induced migration of cancer cells into the tumor environment.

Overall, these results contribute to the understanding of the involvement of HA in nitric oxide-induced cell migration and suggest the potential use of modified HA as a key material in various biomedical applications.

Commenting on the study, Professor Abhay Pandit said: "While recent advances in research on the role of nitric oxide in tumor progression ultimately led to a number of ongoing clinical trials evaluating the effects of NO synthase inhibitors, our focus is on NO itself trying to avoid the side effects/reactions of these inhibitors."

Amir Abdo Alsharabasy received a BSc in Chemistry & Biochemistry, Mansoura University, Egypt, an MSc in Biochemistry, Helwan University, Egypt and an MSc in Biological and Bioprocess Engineering, Sheffield University, UK. He worked for some time as a research fellow in the Radiation Chemistry Department at NCRRT, Egypt. He was recently awarded two prizes for his research. The first was a presentation award at the Second International Conference “Therapeutic Applications of Nitric Oxide in Cancer and Inflammatory Diseases” for his presentation on the interactions between nitric oxide and hemin and their effects on nitration of proteins in breast cancer cells. The second was an EMBO Scientific Exchange Grant to support a visit to Dr. Lasse Jensen at Linköping University, Sweden.

Source:

National University of Ireland Galway

Reference:

Alsharabasy, AM, et al. (2022) Interactions between nitric oxide and hyaluronic acid implicate breast cancer cell migration. Biomacromolecules. doi.org/10.1021/acs.biomac.2c00545.

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