Scientists have discovered why breast cancer cells that have spread to the lungs can ‘wake up’ after years of ‘sleep’, forming incurable secondary tumours. Their research, funded by Breast Cancer Now, reveals the mechanism that triggers this breast cancer ‘time bomb’ and suggests a strategy to defuse it. Patients with estrogen receptor positive (ER+) breast cancer have an ongoing risk of the cancer recurring in another part of the body for many years or even decades after their original diagnosis and treatment. When breast cancer cells spread from the first breast tumor to other parts of the body, it is called secondary or metastatic breast cancer, and while it is treatable, it cannot be cured. The new research, published in the journal Nature Cancer, showed how molecular changes within the lung that occur during aging can support the growth of these secondary cancers.
The team from the Institute of Cancer Research in London has discovered that the protein PDGF-C, which is present in the lung, plays a key role in influencing whether inactive breast cancer cells stay asleep or ‘wake up’. They found that if the level of PDGF-C increases, which is more likely in a lung as it ages or when its tissue is damaged or undergoes scar-like repair, it can cause dormant cancer cells to grow and develop into cancer. to the secondary breast. The researchers then evaluated whether blocking PDGF-C activity could help prevent these cells from “waking up” and secondary tumors from growing. Working with mice with ER+ tumors, researchers at the Breast Cancer Now Toby Robins Research Center at the Institute of Cancer Research have targeted PDGF-C receptor signaling with an anticancer drug called imatinib, which is currently used to treat patients with chronic myeloid leukemia.
The mice were treated with the drug both before and after the tumors developed. For both groups, lung cancer growth was significantly reduced. A study published by another research group demonstrated that PDGF signaling is a key regulator of cells initiating metastasis. This growth factor uses the PI3K-Akt cellular signaling pathway to resist drugs, promote cell renewal, and reorganize the cellular skeleton to promote cell motility necessary for metastasis. By driving the function of these cells, PDGF ultimately promotes stemness and invasion. Blocking the PDGF pathway preferentially reduces lung metastases, but unfortunately does not reduce the primary tumor burden. However, the principle of PDGF signaling antagonism is correct, at least to prevent disease from spreading to the lungs, which are the preferred primary site of metastases.
Dr Simon Vincent, director of research, support and influence at Breast Cancer Now, which funded the study, said: ‘We know that for years after finishing breast cancer treatment many women fear the disease will return. . Up to 80% of primary breast cancers are ER+ and there are around 44,000 cases in the UK each year. With an estimated 61,000 more people living with secondary breast cancer in our country, further research to understand and treat it is vital. This exciting discovery brings us one step closer to understanding how we can slow or stop the development of secondary breast cancer in the lung. It has the potential to benefit thousands of women living with this ‘time bomb’ in the future, ensuring that fewer patients receive the devastating news that the disease has spread.”
- By Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific publications
Turrell FK, Orha R et al. Nat Cancer. 2023 Mar 13.
Ali A, Shafarin J et al. Cell Signal. 2023; 104:110591.
Sen U, Shanavas S et al. Cell Biol Int. 2023; 47(4):742.
Yang L et al. Cell Death Differ. 2020 Jul; 27(7):2066-80.