Circulating tumour cells (CTCs) in the blood of patients with colorectal cancer are a risk factor for later recurrence and metastasis (cancer spread). However, our studies revealed that only one-third of patients with CTCs relapse. This indicates that not all CTCs induce relapse. Increasing evidence suggests that CTCs are heterogeneous (can vary in their form) and have a variable capacity to establish metastases (don’t always spread to new sites in the body). According to the cancer stem cell (CSC) model, most malignancies originate from a small fraction of cancer cells with the properties of stem cells and it is these CSCs which initiate and maintain tumour growth. This suggests that only CSCs in the larger CTC population cause metastasis (cancer spread). We propose that it is cancer stem cells (CSCs) from the primary tumour that are circulating in the blood of colorectal cancer patients which are responsible for recurrence and metastasis. In the proposed project, we plan to identify these cells in liver metastasis using stem cell markers, and to isolate them from blood to confirm their stem cell and metastatic capabilities. We also aim to assess the CSCs in the blood of stage II and III colorectal cancer patients to determine how likely it is that the patients with these cells in their blood will relapse and develop a metastasis.
What we aim to achieve
The proposal has the practical aim of identifying marker(s) of CSCs circulating in the blood of patients with colorectal cancer. The outcomes of our project have the direct potential to radically alter clinical practice for the management of colorectal cancer patients. We aim to monitor early stage colorectal cancer patients for the presence of the CSC markers enabling early intervention treatment. This monitoring will also assist in determining the best treatment option for individual patients. In addition, the markers could be used as a diagnosis tool and may contribute to improved treatment strategies in the long term.
Our next steps and milestones
We aim to develop markers for CSCs circulating in the blood stream of colorectal cancer patients. These can be used for early detection, monitoring and treatment of colorectal cancer. Our next steps include;
(1) Early stage colorectal cancer patients will be monitored more intensely for the presence of the marker(s). If detected, the patients would be subjected to an early intervention using adjuvant chemotherapy and potentially targeted drugs to improve patient outcomes.
(2) Monitoring the level(s) of the marker(s) may also play a vital role in deciding which treatments to give patients with advanced disease and assessing their response to treatments. This has potential cost savings as expensive drugs may be discontinued early if they are no longer effective. This will also allow a better selection of treatment and would lead to reduced risks of long term toxicity in patients who do not have a risk of recurrence. Patients who have an ongoing stable level of the marker(s) may simply require a low level maintenance therapy thereby reducing the toxicity and cost. With the trend to ongoing/maintenance systemic therapy, the absence of the marker(s) may identify patients who can have chemotherapy 'holidays', resulting in benefits of no toxicity, improved quality of life and cost savings.
(3) If a rising level of the marker(s) is shown to predict disease progression, the findings have the potential to replace the need for expensive radiological assessment for metastasis, with a minimally invasive and cost-effective blood test for the presence of the marker(s). Thus outcomes of the project will be at two levels. These outcomes include earlier diagnosis of metastatic colorectal cancer and its control. In the short term, we expect to provide the marker(s) of CSCs circulating in the blood of colorectal cancer patients as an early indicator of impending metastatic disease. In the medium term, the marker(s) may be developed as a minimally invasive and cost-effective blood test for impending metastatic colorectal cancer. In the long term, more specific, selective or potent means of inhibiting the growth, invasion and resistance to apoptosis (cell death) of cancer stem cells may be developed. These, in turn, may lead to clinical programs thereby significantly improving the outcomes.
What motivates me
I have a passion for cancer research.
My message to supporters
Understanding the mechanism of metastasis of colorectal cancer is a challenging task and further studies are required to unravel it.