Important discovery advances the fight to reduce breast cancer recurrence

In a search for new ways to fight breast cancer, scientists at Duke-NUS Medical School have uncovered the surprising role of a protein commonly associated with cancer growth. They discovered that in estrogen receptor-positive (ER+) breast cancer, this protein acts as a tumor suppressor instead.

ER+ breast cancer accounts for about 80% of all breast cancer diagnoses, yet almost 50% of women diagnosed with it experience a relapse after initial treatment.

The unexpected finding refutes the long-held view that the protein Gα13 acts as an accelerator of cancer cell growth, as seen with similar G proteins. This latest discovery, published in the journal Breast cancer researchis the first study to identify Gα13 as a tumor suppressor in solid tumors. This could lead to new personalized approaches in breast cancer treatment by examining the levels of Gα13 and other proteins.

Dr. Lalitha Subramanyan, a Duke-NUS graduate and now a postdoctoral fellow in the Department of Pharmacology and Cancer Biology at Duke University, the first author of the study, said: “Our findings challenge the previous notion that Gα13 generally promotes cancer growth across different tumor types. Instead, we found evidence that Gα13 may help interrupt harmful signaling pathways in estrogen receptor-positive breast cancer, potentially slowing or stopping the growth of cancer cells.

“This makes the discovery of the protective role of Gα13 even more significant, as it fills a critical gap in our understanding of how different molecular pathways contribute to cancer development.”

The study's findings provide grounds for new treatment strategies. Associate Professor Yap Yoon Sim from the Department of Breast and Gynaecological Oncology at the National Cancer Center Singapore, who was not involved in the research, said: “It is interesting that the effects of the GNA13 protein are different in different types of breast cancer cells.”

“These findings underscore the complexity of cancer biology and the need to understand the role of different molecules and pathways in different contexts. It is hoped that this knowledge may facilitate the development of new strategies to treat breast cancer in the near future.”

Despite various advances in treatment, breast cancer is still the most commonly diagnosed cancer worldwide and one of the leading causes of cancer-related deaths in women. In 2020, approximately 685,000 people died from breast cancer.

In Singapore, breast cancer is the most common cancer among women. According to the Singapore Cancer Society, breast cancer accounts for almost one in three cancer diagnoses among women, highlighting the profound impact of the disease on women's health as well as the urgent need for more effective treatments.

Breast cancer is a complex disease that consists of different types and responds to different treatments. The treatment approach varies depending on the molecular subtype.

Gα13 acts as a messenger within cells, carrying signals from the cell surface to the cell interior and triggering a cascade of reactions that affect the cell's behavior, including its growth, division, and response to its environment. The study's findings reveal a previously unknown link between Gα13 signaling and that of the hormone estrogen, a key factor in breast cancer. Together, they control a key oncogene, MYC, and the growth of cancer cells.

Associate Professor Mei Wang from the Cancer and Stem Cell Biology Program at Duke-NUS and co-author of the study commented: “Our findings not only advance our understanding of Gα13 and related proteins in cancer development, but also provide a new perspective for the targeted treatment of recurrent ER+ cancers.”

“While treatment of ER+ breast cancer primarily targets ER signaling, nearly half of these patients develop resistance to such therapy over time. The discovery of Gα13 control of estrogen signaling and MYC function offers new opportunities to counteract resistant ER+ breast cancer.”

During the study, a correlation was also observed between lower Gα13 levels and worse survival in patients with ER+ breast cancer, further supporting the protective role of Gα13 against ER+ breast cancer.

The researchers plan to expand their study to investigate the role of Gα13 in other hormone-sensitive cancers and apply these principles to other solid cancers.

Professor Patrick Tan, Senior Vice Dean for Research at Duke-NUS, added: “This study represents a clear and significant advance that has potential implications for cancer treatment strategies. Understanding these molecular mechanisms paves the way for the development of targeted drugs that could improve the effectiveness of breast cancer treatments and ultimately improve survival rates and quality of life for those affected by this devastating disease.”