Dr Andrzej Rutkowski, Lead Scientist at Medicines Discovery Catapult (MDC), illuminates the value of this pioneering approach.
Circulating tumour DNA (ctDNA) analysis in liquid biopsies addresses an array of questions pivotal for cancer research and treatment.
Benefits of the Circulating tumour DNA (ctDNA) technique include:
All these insights are derived from simply a few millilitres of blood, making liquid biopsies quicker, less expensive, and safer than conventional biopsies. Most impressively, they capture DNA shed from the entire body, offering a broad and in-depth perspective. Along with its low risk and cost, high data yield, and comprehensive coverage, this tool is ideal for longitudinal monitoring of patient response, remission, or relapse.
Depending on the research question, Circulating tumour DNA (ctDNA) can be analysed in two ways:
The genes KRAS and BRAF, which control growth and division of normal cells, are at the epicentre of genetic alterations in cancer, with widespread mutations turning these genes into serious disease accelerators. BRAF often fuels the disease with one notorious mutation, scientifically designated as V600E, while KRAS has a more kaleidoscopic spectrum of genetic transformations that render it into an active oncogene. Striding forward in our advanced research, MDC successfully replicated and validated multiplex droplet digital PCR assays. These assays zero in on the formidable BRAF V600E mutation and fourteen high-frequency KRAS mutations.
Our team of experts recently used these multiplex assays in a project with an MDC partner that involved the analysis of longitudinal samples from a phase I drug trial. Genetic mutations were found in the diagnostic samples and even identified a new KRAS mutation
Our multiplex assays facilitate the study of fourteen KRAS mutations using merely three reactions rather than one for every mutation. This eliminates the dilemma of how to best utilise the limited Circulating tumour DNA (ctDNA) sample.
You might be thinking, “Well, this isn’t ground-breaking – I’ve seen KRAS G12/G13 screening kits out there doing a similar job.” True, these kits do test for the most prevent mutations all in one go. However, while they can confirm that your sample contains a mutation, they focus on only the top few mutations, and they fall short at pinpointing exactly which mutation that is. This distinction could hold the key in discerning cancer’s genetic makeup and, consequently, its strongest or weakest point.
At MDC, we provide tailored and differentiated tests rather than generic services. Whether you’re focusing on BRAF and KRAS driver mutations or any specific set of gene mutations, our extensive experience in digital PCR assay design and validation enables us to develop bespoke digital assays to address your research needs.
Multiple companion diagnostic tests are already green-lighted for pinpointing cancer-driving mutations in Circulating tumour DNA (ctDNA). They play a crucial role in identifying the cohort of patients with the highest odds of responding to a particular treatment. This strategic approach optimises resource allocation, saving substantial time and money. But beyond material resources, crucially it spares patients from the physical tolls of ineffective therapies. So, it’s not just about enhancing healthcare efficiency, it’s about reinforcing patient-centric care where wellness and well-being take centre stage.
By leveraging this advanced technology with MDC support, you can strategise patient stratification, treatment and monitoring more effectively in your drug development efforts.
2-Dimensional plots showing the detection of the top 14 cancer driver mutations in KRAS
2-Dimensional plots showing the detection of the top 14 cancer driver mutations in KRAS
2-Dimensional plots showing the detection of the top 14 cancer driver mutations in KRAS
An example of MDC’s ddPCR assay identifying an additional emerging KRAS mutation in a patient sample.
Longitudinal mutation burden in patients
Preclinical to clinical, building a translational link between in vitro and in vivo models of neuroinflammation for drug discovery.
