Within five years of starting therapy, women with early-stage breast cancer have a 7% to 11% probability of experiencing a recurrence; for patients with more advanced stages of the disease, this percentage may be greater. Even while chemotherapy tries to eradicate every cancer cell, some may manage to escape and live, which might lead to the disease returning.
The researchers discovered that when they examined blood and tumor samples from 63 patients with various stages of breast cancer, lab-grown breast cancer cells, and laboratory models, cancer cells that expressed high levels of a particular molecule—a small non-coding RNA called miR-125b—cooperated with surrounding cancer cells to help the latter proliferate and resist chemotherapy.
This ground-breaking study demonstrates that cancer cells exhibit altruistic behavior to assist other cancer cells grow by sacrificing their own capacities to expand, defying the commonly held notion that they are just self-serving and motivated by their own survival. This finding suggests that breaking up this kind of collaboration could be essential to creating breast cancer medicines that work better.
“Our research has identified these cooperative behaviors between cancer cells, which treatment must target specifically to destroy them more effectively,” Assistant Professor Leong stated. Treatment strategies, for instance, must include mechanisms that stop the cancer cells around the “self-sacrificing” cells from reacting and reaping the benefits.”
The study, which was published in Molecular Cancer, explains how the intricate signaling pathway in these selfless cells causes the tumor to become resistant to therapy in general.
Altruistic cancer cells with elevated miR-125b expression experience decreased proliferation through the NF-κB signaling pathway. Ironically, the very signaling pathway that causes these selfless cancer cells to produce IGFBP2 and CCL28 proteins also causes them to release other substances that increase the cancer tumor’s overall resistance to chemotherapy.
“Taking out these selfless cancer cells could be a possible therapeutic approach. We might, however, need to take these cells’ longevity into account. The study’s first author and research fellow from the Department of Pathology at NUS Medicine, Dr. Muhammad Sufyan Bin Masroni, said, “We found that despite the self-sacrifice, the altruistic cancer cells can regenerate from the non-altruistic ones and remain within the tumor population at a low yet consistent frequency.”
The research team also included collaborators from the NUS Faculty of Science, the Institute of Molecular and Cell Biology (IMCB) at the Agency for Science, Technology and Research (A*STAR), MiRXES, CellSievo, Raffles Hospital, Tucker Medical, and the Pennsylvania State University in the United States, as well as other departments at NUS Medicine, Nanyang Technological University, Singapore (NTU), and Singapore Institute for Clinical Sciences (SICS).
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