Host phenotypes based on body composition and systemic inflammation provide highly prognostic information in patients with cancer but are not specifically targeted during cancer therapy. Patients with a combination of myosteatosis and systemic inflammation have a particular poor survival. The aim of this project is to assess the role of insulin resistance as a main driver of adverse host phenotypes in cancer.
I am grateful to the World Cancer Research Fund for supporting this novel translational study. The findings will highlight the importance of using patient characteristics alongside tumour characteristics in cancer treatment, will help unravel the underlying mechanisms behind adverse host phenotypes in cancer, and might yield potential new targets for therapy in the future.
Dr David van Dijk
Background
The accumulation of fat in unusual areas like muscles (known as myosteatosis) and the liver has been found to be closely linked to how long these patients survive, independent of the stage of their cancer. Patients with a particular combination of characteristics: high levels of inflammation (measured by a marker called CRP) and myosteatosis have even poorer survival rates. Interestingly, these “adverse host characteristics” can predict survival better than just looking at the tumour itself. This suggests that understanding these characteristics might be crucial for predicting and improving outcomes for patients with colorectal cancer.
Research aims
The main idea being explored is whether insulin resistance, a condition where the body’s cells don’t respond well to insulin and thus struggle to take up blood sugar, is behind the fat buildup seen in these patients. The hypothesis is that inflammation triggered by the tumour could be causing insulin resistance, leading to fat being stored in muscles rather than in the usual places like fat tissue. This process might worsen the prognosis.
The study aims to investigate this hypothesis further. Thirty-six patients that will undergo surgery for colorectal cancer that has spread to the liver will participate in this study. These patients will be divided into two groups based on their CT scans and blood tests: one group with high inflammation and myosteatosis, and another with low inflammation and no myosteatosis.
Methodology
To assess insulin sensitivity, which is how well the body responds to insulin, a special test called a c will be used. This test involves infusing insulin into the patient’s bloodstream at a constant rate while keeping their blood sugar level steady. By measuring how much glucose is needed to maintain the steady blood sugar level, precise measurements on how sensitive the patient’s cells are to insulin can be made. During liver surgery, tissue samples from the liver, muscles, and fat, as well as blood samples will be taken to analyse fat buildup and inflammation in these tissues.
Potential impact and importance of the study
If the study confirms that insulin resistance is linked to fat buildup and inflammation in colorectal cancer patients, it could open up new avenues for treatment. Targeting insulin resistance directly using existing diabetes drugs or indirectly through anti-inflammatory medications could potentially improve survival rates in these patients. Moreover, the study aims to streamline future research and clinical trials by utilizing already developed technology to analyse body composition and by leveraging existing treatments developed for conditions like obesity, which share similar underlying mechanisms with insulin resistance and inflammation. This could accelerate the development of effective treatment strategies for colorectal cancer patients with these adverse host characteristics.