University of Pretoria: Cell tests show the potential of epigenetic therapy to treat breast cancer

Researchers at the Faculty of Animal Science and Food Engineering (FZEA) at USP, in Pirassununga, identified the antitumor potential of molecules in a new approach, epigenetic therapy. Epigenetics is linked to the biochemical mechanisms that regulate gene expression, without changes in the DNA sequence.

The results are still experimental, obtained in tests with breast cancer cell cultures. However, according to Professor Heidge Fukumasu, the study’s advisor, the experiments open space for the development of various therapies for the treatment of tumors in animals and also in humans.

The work is considered innovative for implementing techniques little used in veterinary oncology. Responsible for the research, biologist Pedro Luiz Porfirio Xavier says that epigenetic therapy is already well described in human medicine, but little in veterinary medicine, and that it is an alternative to “fix the altered expression of some genes associated with the characteristics of cancer, like malignity”.

The study conducted by Xavier gained prominence for addressing epigenetics and cancer in dogs, a little studied topic, and being awarded the Capes 2021 Thesis Award in the Veterinary Medicine area of ​​the Graduate Program in Animal Bioscience at USP.

Epigenetic disorders, says Xavier, are associated with the development and progression of cancer, but “unlike genetic alterations, epigenetic disorders can be reversible and this opens up a series of therapeutic possibilities”. The team from the Laboratory of Comparative and Translational Oncology (LOCT) managed to inhibit the function of “ defective proteins ”, making cancer cells “less malignant and even more susceptible to conventional therapy, such as chemotherapy”, says the researcher.

In the first part, Xavier’s studies focused on the epigenetics of cancer in dogs, comparing it with the findings already described in the literature on the epigenetics of tumors in humans. The results, according to the researchers, show that veterinary oncology has much to benefit from the epigenetic knowledge of humans and that the similarities “highlight dogs as an excellent model for studying human oncology”, assures Xavier, stating that this is a topic they call comparative oncology.

Then, they performed laboratory tests ( in vitro) with cell culture slides from canine mammary tumors. These cells were “exposed to different molecules that have therapeutic potential against cancer”, says the researcher. They carried out a series of experiments until they came up with a “molecule that was very effective in decreasing the malignancy of breast cancer cells in dogs”, JQ1, which inhibited a class of epigenetic proteins called BET. Now, the team intends to deepen the studies in an in vivo model and “in the future in dogs that have this disease”.

And the study gained a final chapter with tests for a new inhibitor of epigenetic proteins, this time in human breast tumor cells. The new molecule is called TW09 and was recently developed by scientists Stefan Knapp and Susanne Müller, from Goethe University, Frankfurt, Germany, where Xavier was an intern. According to the researcher, the results showed that TW09 decreases tumor viability and potential, “inhibiting the proliferation and tumorigenicity [capacity or tendency to produce or develop tumors] of breast cancer cells.”

Breast cancer is more common in dogs and cats than in humans. According to the Federal Council of Veterinary Medicine, the tumor affects 45% of canine females and 30% of felines. Of women diagnosed with cancer in Brazil in 2020, 29% had breast tumors, according to the National Cancer Institute. The work routine of the LOCT involves research on breast cancer, lymphomas and sarcoids in dogs, cats and even horses.