The study, published in the European Journal of Pharmacology, provides “new ways for the treatment of the special type of breast cancer called the triple-negative breast cancer,” according to the research’s corresponding author, Prof. Raafat El-Awady.

Triple-negative breast cancers are more aggressive than other forms of breast cancer as they tend to grow and spread quickly, have limited treatment options and show resistance to available therapies.

“Our research has found that high HDAC6 levels lower the amount of progesterone receptors, making breast cancer cells less responsive to hormonal therapies,” Prof. El-Awady, a pharmacologist, adds.

“The implications of our research could extend beyond the lab, offering hope for more effective treatment options in the battle against aggressive breast cancer.”

HDAC6 or histone deacetylase 6 influence a broad range of signalling pathways and cellular processes in cancer cells involving response of cancer cells to therapeutics, and cancer metastasis, or development of malignant growth beyond the tumour’s primary site, while hormone receptors, like the oestrogen and progesterone, cause the growth of only some types of breast cancers, which are hormone dependent.

But when these receptors do not function properly, according to Prof. El-Awady, breast cancer patients often struggle to respond to common hormonal therapies, leaving them with limited treatment options.

Prof. El-Awady described triple-breast cancer as “a type (of cancer) that lacks these hormone receptors and is aggressive and hard to treat. Hormone receptors, like the oestrogen and progesterone receptors, play a significant role in how breast cancer grows and responds to treatments.

“When these receptors are not expressed or do not function properly, breast cancer patients often struggle to respond to common hormonal therapies, leaving them with limited treatment options.”

The main practical goal of the research is to identify a new therapeutic strategy to enhance the sensitivity of aggressive breast cancer cells to hormonal therapies, and the authors highlight HDAC6 as a potential therapeutic target, demonstrating how inhibiting this protein can restore progesterone receptor levels and potentially reverse resistance to hormonal treatments.

“By shedding light on the role of HDAC6, we aimed to provide insights that could pave the way for developing more effective treatments for patients, particularly those with challenging breast cancer subtypes that are difficult to treat,” says Prof. El-Awady.

The scientists claim that one best way to combat triple-negative cancer is by using a medicine with the ability to stop HDAC6, a process that can lead to a surge in the levels of progesterone receptors.

“By using a drug that blocks HDAC6, we were able to boost the levels of progesterone receptors in breast cancer that were previously lacked it. This change made the breast cancer cells more sensitive to common hormonal therapies.

“These findings suggest that targeting HDAC6 could enhance the effects of hormonal therapies, offering a new hope for patients, particularly those with aggressive types like the triple-negative breast cancer, which is typically aggressive and more difficult to treat,” Prof. El-Awady added.

Statistics show that breast cancer is the most prevalent type of cancer among women worldwide, with 2,296,840 new cases of breast cancer in 2022.

Dr. Wafaa Ramadan, a molecular medicine specialist and the study’s first author, said the research stands out in its discovery that high levels of HDAC6 are linked to low amounts of the progesterone receptors in tissues of breast cancer patients.

“This indicates that the presence of active HDAC6 leads to a reduction or loss of the progesterone receptors with subsequent resistance to anti-progesterone therapies.

“Most importantly, we found that by blocking HDAC6, breast cancer cells became more sensitive to hormonal therapies. This is especially important for types of breast cancer that are more challenging to treat like the triple negative breast cancer.”

The research, says Dr. Burcu Ilce, a specialist in bioinformatics and functional genomics and a co-author, opens up new ways for breast cancer treatment strategies.

“By understanding the role of HDAC6 in hormone receptor regulation, we can potentially develop targeted therapies that enhance the effectiveness of existing treatments.

“This approach is crucial for patients who may not respond to standard hormonal therapies, as it offers a new avenue for tackling their disease. Consequently, targeting HDAC6 could lead to better treatment outcomes, reduced resistance to therapies, and improved survival rates for patients with challenging forms of breast cancer.” Prof. Maha Sabre-Ayad, a Clinical Pharmacologist and a co-author, adds.

The scientists say they hope for their findings to significantly advance personalised cancer therapy, offering new hopes for patients with limited treatment options.

“Given the growing focus on targeted cancer therapies and epigenetic drugs, it is likely that pharmaceutical companies and biotech firms could be interested in further exploring the development and clinical testing of HDAC6-targeted therapies,” said Varsha Menon, a co-author and research assistant.

“This interest could open the door to strategic partnerships that would accelerate the translation of our research into impactful therapies for breast cancer patients, particularly those with hormone receptor-negative or resistant tumours.”

Prof. El-Awady notes that once the research findings are translated into clinical practice by targeting HDAC6, “they could enhance treatment outcomes for patients with hormone receptor-negative breast cancer.

“By restoring or increasing hormone receptor expression, this approach could provide new therapeutic options, improving treatment efficacy and potentially increasing survival rates for patients who currently have limited responses to conventional hormonal therapies”.

Added Prof. Iman Talaat, a clinical pathologist and a co-author.

“We are excited about the possibility that our work related to targeting HDAC6 could lead to breakthroughs in how we treat breast cancer, giving hope to patients who may have limited treatment options.”

Source: University of Sharjah