Accumulating research suggests that the best possible treatments for cancer will not simply target and kill cancerous cells but will also work by making the neighboring cells—the so-called tumor microenvironment—behave more normally.
“Most people recognize that cancer is not just a ball of malignant cells. It’s a complex rogue organ,” says Frances Balkwill, Ph.D., professor of cancer biology at Barts Cancer Institute, Queen Mary University of London. “At least half the tumor isn’t made up of malignant cells at all. It’s all the other cells of the host, particularly immune system cells, fibroblasts, and blood vessel cells, that are recruited and often corrupted by the malignant cells to help the tumor itself grow and spread.”
Dr. Balkwill and her group study the role of tumor microenvironment signaling proteins—cytokines and chemokines—in human high-grade serous ovarian cancer. One of their targets is the cytokine receptor interleukin 6 (IL-6), a known tumor promoter.
“We’ve done one small clinical trial, and now we’re back in the lab trying to learn from that clinical trial about how we might use anti-IL-6 in combination with other cancer treatments,” explains Dr. Balkwill. “[We’re exploring the idea of] blocking cancer-related inflammation, which would help other treatments to work.”
Another target is the chemokine receptor CCR4. “When we use a small molecule or an antibody against CCR4 in mouse models, we find that it seems to switch macrophages from being tumor promoting to being tumor inhibiting, and it has anticancer effects,” notes Dr. Balkwill. This research, which Dr. Balkwill’s lab is carrying out in collaboration with Cancer Research UK and AstraZeneca, is studying the therapeutic potential of a small molecule CCR4 inhibitor. Dr. Balkwill anticipates that the compound will be evaluated next year in a Phase I trial in patients with advanced renal cancer.
Besides this work, Dr. Balkwill’s group is also trying to build a completely human tumor model. “We are deconstructing the tumor microenvironment of peritoneal metastasis of high-grade serous ovarian cancer,” explains Dr. Balkwill. “We are trying to rebuild as much as we can of that microenvironment in a way that uses stem cell biology, tissue engineering, and biomechanics in a multidisciplinary project.”