New research conducted by scientists at UCL and Yale suggests that the presence of healthy cells within tumors can hinder the effectiveness of chemotherapy. These findings, published in the journal Cell, provide insight into why some patients with bowel cancer may experience poor outcomes.
Bowel cancer is responsible for the deaths of over 900,000 people annually and ranks as the second leading cause of cancer-related mortality worldwide. In the UK, it accounts for approximately 10% of all cancer deaths.
In the first study, researchers at UCL utilized cutting-edge single-cell analysis technology to study the behavior of 1,107 “mini-tumors” derived from mice. This analysis revealed that bowel cancer cells can exist in either a fast-growing or slow-growing state, and that the presence of healthy cells can push cancer cells towards the slow-growing state. As chemotherapies primarily target fast-growing cells, the slow-growing cancer cells are more likely to be resistant to treatment.
Dr. Chris Tape, a senior author of the studies from UCL Cancer Institute, explained, “Recent research has shown that bowel cancer patients with an abundance of healthy cells in their tumor, such as fibroblasts involved in wound healing, often have a poor prognosis. However, the reason behind this association was not known until now. Our research suggests that because chemotherapies primarily target fast-growing cells, cancer cells that have their growth slowed down by healthy cells become less sensitive to chemotherapy.”
In the second study, the researchers sought to confirm their findings using human cells. They analyzed over 2,500 mini-tumors grown from donated tissue from patients who had undergone bowel cancer surgery. The results showed that factors such as patient age and specific mutations in the tumor did not significantly affect the response to chemotherapy. The crucial factor was the rate of cancer cell growth. Importantly, healthy fibroblast cells were capable of slowing down cancer growth in certain patients, rendering the cancer cells completely resistant to chemotherapy.
Dr. Maria Ramos Zapatero, a first author of one of the studies from UCL Cancer Institute, stated, “The slow-growing state observed in these bowel cancers is highly unusual and typically only found during fetal development or following intestinal tissue damage. The presence of fibroblasts in healthy tissue appears to stimulate cancer cells to enter a defensive state, which protects them from chemotherapy. This transformation happens rapidly, often within hours, explaining why treatment fails to work. The cancer cells sustain damage but do not die.”
Professor Smita Krishnaswamy, a senior author of one of the studies from Yale University, remarked, “Previous technical limitations meant that researchers could only analyze a limited number of scenarios at a time when studying single-cell behavior in cancer cells and their surrounding environment. However, recent advances in mass cytometry workflow and the computational method called TRELLIS have allowed us to analyze thousands of variables, including different cancer cell mutations, therapies, and the complex interaction between tumors and surrounding cells. These technical breakthroughs have enabled us to gain a comprehensive understanding and explain why certain cancers are less responsive to treatment.”
According to the researchers, finding ways to induce fast-growing states in cancer cells before chemotherapy treatment may enhance the effectiveness of the treatment. Dr. Tape concluded, “By comprehending the molecular processes that drive this transformation, we may be able to develop strategies to disrupt communication between cancer cells and healthy cells, thereby reverting the tumor to its fast-growing state and making the cancer cells responsive to chemotherapies even in the presence of healthy cells. This discovery opens up a significant opportunity to improve outcomes for patients with bowel cancer that is difficult to treat.”
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
