Study offers hope for safer chemotherapy era in breast cancer

Breast cancer is the deadliest and most common type of cancer in women. Treatment options often require the administration of anti-cancer drugs in high doses, as cells develop resistance to chemotherapy, causing painful side effects in patients. Recently, researchers have identified that lowering the level of a protein called DSS1 can increase patients’ responsiveness to chemotherapy, thereby reducing doses of the drug as well as the risk of side effects in patients.

Immunohistochemistry showing DSS1 and PCID2 in normal and cancerous breast tissue – While PCID2 was still expressed, DSS1 expression was higher with increased level of malignancy. Image courtesy: Kazuhiko Kuwahara of Fujita Health University

Each year around the world, more than 600,000 women die from fatal breast cancer, the most common cancer in women. While the individual or combined effects of lifestyle and environmental factors contribute to the development of breast cancer in a large percentage of the female population, the formation of malignant tumors is usually associated with genetic factors. For example, BRCA1 and BRCA2 are two genes that impact a person’s chances of developing breast cancer. Under normal conditions, the protein products of these genes help repair DNA damage, reducing the chances of uncontrolled cell growth and tumor development. Any “mutation” or anomaly at the cellular level that interferes with the functioning of the BRCA The genes thus predispose the person to a higher risk of developing breast cancer.

Thus, for decades, researchers have endeavored to decipher the role of BRCA genes and cellular components associated with the BRCA1 and BRCA2 proteins to understand the progression of breast cancer and to design appropriate targeted therapies to prevent and treat the disease. Today, a group of collaborating researchers in Japan and the United States have successfully identified a cell machinery protein associated with BRCA that plays a critical role in the progression of breast cancer. The eminent researchers who were part of this research project were Kazuhiko Kuwahara (Fujita Health University School of Medicine, Japan), Naomi Gondo (Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan), Yasuhiro Sakai (Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan), Zhenhuan Zhang (Department of Radiation Oncology, University of Florida, Gainesville, FL) and Andri Rezano (Department of Biomedical Sciences, Division of Cell Biology, Faculty of medicine, Universitas Padjadjaran, West Java, Indonesia). The findings of the study, recently published in Laboratory investigation, also offer important avenues for the development of targeted therapy for this deadly disease.

In their study, the researchers began by taking a close look at a protein complex called TRanscription-EXport-2 (TREX-2), which is involved in the transcription and export of mRNA from the nucleus. The complex is made up of several proteins, such as GANP, PCID2, DSS1, and centrin, and according to previous reports, the aberrant expression of some of these proteins leads to DNA damage which results in tumor formation. Dr. Kuwahara, the corresponding author of the study, explains what prompted them to look at the TREX-2 complex proteins, “Previously, we observed that GANP deficiency was closely associated with breast carcinogenesis. We are therefore interested in other protein components of the TREX-2 complex for their possible association with breast cancer.. “Based on the available published information, they focused on DSS1, a protein known to be associated with stabilization of the BRCA2 protein in human cell lines.

To test their hypotheses, the researchers conducted a series of studies that began by verifying the expression levels of various TREX-2 complex proteins, including DSS1, in breast cancer tissues, followed by experiments at cellular. They found that DSS1 protein expression was higher in human breast carcinoma tissue than in normal tissue. In contrast, expression of the PCID2 protein was normal in malignant tissues. They also found that low expression of DSS1 is associated with longer survival time in patients. Interestingly, breast cancer cells with decreased DSS1 levels were more sensitive to standard anticancer drugs DXR and PTX, while an elevated level of DSS1 made breast cancer cells resistant to these therapeutic agents.

The results marked a breakthrough in breast cancer treatment research. Dr Kuwahara sums it up: “The strong side effects of cancer therapies add to the suffering of the patients and complicate the treatment modalities. Our research suggests that depletion of the DSS1 protein in breast cancer cells can make cells chemosensitive, that is, more sensitive to lower doses of anti-cancer drugs, which means the risks of side effects. induced by drugs in breast cancer patients will be reduced by this. technical. “

The promising result of this study raises the hope of a safer chemotherapy era in the near future for breast cancer patients.