Beatson Cancer Charity awarded a £16,870 research grant to Douglas Cartwright (Clinical Research Fellow at the CRUK Beatson Institute for Cancer Research) for conducting a spatial analysis of cancer associated fibroblast subtypes in high grade serous ovarian carcinoma.
Due to the lack of symptoms in the early stages of ovarian cancer, most women are diagnosed late once the cancer has spread, making it incurable. Most women have a form of ovarian cancer, called high-grade serous ovarian cancer, that responds well to initial treatment with chemotherapy and surgery. However, the cancer eventually grows back, and subsequent treatment becomes less effective to the point where existing treatments cannot control the disease.
A tumour is not just made up of cancer cells, but also of non-cancerous cells that surround the dividing cancer cells. One of the reasons why subsequent treatments are less effective is that cancer cells can ‘hijack’ these noncancerous cells to support their growth and resist the toxic effects of chemotherapy. To counteract this, Douglas and his colleagues aim to develop treatments that disrupt the signals between cancer and non-cancerous cells.
One of the main types of non-cancerous cells that supports tumour growth is called a cancer-associated fibroblast (CAF). They make up a large proportion of cells within a tumour in high-grade serous ovarian cancer. However, there are many types of cancer associated fibroblasts and they have different effects within a tumour, some of which can even prevent cancer growth. Research from Douglas and his colleagues shows that there are unique types of cancer associated fibroblasts at the original site of the cancer and in different organs to which the cancer has spread. Douglas and his colleagues also found that chemotherapy treatment can alter the cancer-associated fibroblasts within cancer. To develop treatments targeted against cancer-associated fibroblasts, researchers need to understand which cell types have the most effect on how the tumour grows and how it responds to chemotherapy.
Cancer-associated fibroblast types can be difficult to identify with existing laboratory techniques as they have no unique markers or features that distinguish one type from another. However, a new technology (CODEX Staining) allows researchers to stain slices of tumour tissue, obtained from patients when they undergo surgery, for up to 40 different markers or features. Researchers can then analyse images of these tumour slices through a spatial analysis which enables them to accurately identify different types of cells within the tumours. By performing this analysis on large collections of tumour samples, researchers can detect patterns that are associated with poor response to treatment and design drugs to combat this.
*Example images of multiplex staining highlighting cancer cells (green) and two cancer associated fibroblast markers, FAP (yellow) and αSMA (red).*
In this study, a spatial analysis will be conducted on ovarian cancer tumour samples obtained from NHSGGC patients and patients who participated in previous clinical trials.
The data from this study will enable researchers to understand which cell types have the most effect on how a tumour grows and how it responds to chemotherapy. It will also provide the basis for a larger study proposal to develop new drug combinations that target supporting cells in ovarian cancer tumours. Douglas and his colleagues hope to find drugs that are already in clinical use for other conditions that can be repurposed for use in ovarian cancer. This would allow clinicians to rapidly apply these treatment combinations in clinical use.