Understanding the mechanisms of treatment resistance in colorectal cancer using organoid models

点击翻译按钮获取中文摘要

Colorectal (bowel) cancer affects more than 45,000 people in the UK each year, and only about 50-60% of people treated for bowel cancer survive 5 years after being diagnosed. One of the ways to improve the survival of patients with bowel cancer is by giving chemo and/or radiotherapy to shrink the cancer down before any surgery is carried out. This is known as "neoadjuvant therapy" and has been used a lot for patients with cancer affecting the last bit of the bowel (the back passage). It has only recently been found in a research study called FOXTROT that it may be effective in patients with cancer in other parts of the bowel (the colon) as well. Despite these advances, this type of treatment only leads to substantial shrinkage of the cancer in approximately 10-20% of patients. We would like to improve this, as in patients where a lot of shrinkage occurs they do much better than patients who do not get any shrinkage. I have carried out research in cancer of the back passage that shows two potential ways we could increase the shrinkage by giving two different, very new, drug therapies in addition to the standard treatment. We have found this by making "mini-avatars" called organoids, which are cancers grown in the laboratory from a specimen of the patient's cancer. These undergo exactly the same response to treatment in the laboratory as the patient would experience when their cancer is treated. I would like to expand the research I have done by growing more models of colon cancer, and then using them to simulate neoadjuvant treatment and then analyse them using genetic sequencing. This will allow us to understand what makes them resistant to treatment, and then identify new treatments (chosen by expert oncologists) that may make them more sensitive. We can then re-treat the resistant models with these new drugs to see if they work.Through this, we hope to further increase the benefit of treatment given before surgery to patients, increasing survival from bowel cancer and reducing some of the toxicity seen in patients by picking the correct treatment for them.