SINGAPORE: In a groundbreaking study spanning over a decade, a National University of Singapore (NUS) team has uncovered a novel aspect of breast cancer behaviour that could revolutionize treatment strategies.
The study, which aimed to understand why certain breast cancer tumours exhibit resilience to chemotherapy and lead to recurrence in patients even after initial treatment, was conducted by Research Assistant Professor Leong Sai Mun and his research team at the NUS Centre for Cancer Research and the Department of Pathology at the Yong Loo Lin School of Medicine.
For patients with early-stage breast cancer, there exists a 7 to 11 per cent chance of relapse within five years post-initial treatment. This risk is even higher for patients with more advanced stages of the disease. Despite the goal of chemotherapy to eradicate all cancer cells, some manage to survive, causing a relapse.
The research team examined tumour and blood samples from 63 breast cancer patients at various stages, as well as lab-grown breast cancer cells and laboratory models.
Their findings revealed a crucial factor—cancer cells with high expression of a specific molecule, a small non-coding RNA known as miR-125b, exhibited altruistic behaviour. Contrary to the prevailing belief that cancer cells are solely self-serving, these altruistic cells cooperated with surrounding cancer cells, fostering their growth and resistance to chemotherapy.
Asst Prof Leong emphasized the significance of this discovery, saying, “Our research has identified these cooperative behaviours between cancer cells, which treatment must target specifically, for them to be destroyed more effectively. For example, treatment methods have to incorporate mechanisms that prevent the surrounding cancer cells from responding and benefiting from the ‘self-sacrificing’ cells.”
Published in the Molecular Cancer journal, the research paper delves into the intricate signalling process within these altruistic cells, elucidating the tumour’s overall resistance to treatment. The signalling pathway, known as NF-κB, induces reduced proliferation in altruistic cancer cells with high miR-125b expression. Paradoxically, this pathway prompts these cells to release substances—IGFBP2 and CCL28 proteins—enhancing the tumour’s tolerance to chemotherapy.
Dr Muhammad Sufyan Bin Masroni, the first author of the study and research fellow from the Department of Pathology at NUS Medicine, highlighted a potential treatment strategy, saying:
“Removing these altruistic cancer cells can be a potential treatment strategy. However, we may have to consider the persistence of these cells. We found that despite the self-sacrifice, the altruistic cancer cells can regenerate from the non-altruistic ones and remain within the tumour population at a low yet consistent frequency.”
Associate Professor Mikael Hartman, the study’s co-author, commended the research’s importance and said, “This research study provides important insights into the intricate biology of breast cancer, offering a promising avenue for better comprehension of its behavioural aspects, prognosis, and potential treatment targets.”
This breakthrough study opens new doors for developing more effective breast cancer treatments by targeting and disrupting the altruistic behaviours of cancer cells, shedding light on the complex interplay within tumours and paving the way for improved prognoses and treatment outcomes.