How PointMan™ Testing Kits Could Advance Non-Invasive Cancer Diagnostics

Dr Del Sol has been using Pointman™ technology since 2013  About Dr Del Sol Dr Del Sol obtained his BSc Microbiology Hons degree at Havana University, and joined the Streptomyces Genetics research lab at the Centre for Pharmaceutical Chemistry in Havana, Cuba. After a year at the National Centre of Biotechnology in Madrid, Spain, he moved to Swansea University to complete his PhD in the field of molecular microbiology. A few years later, he was appointed as Lecturer in Genetics at the College of Medicine, in Swansea University.

Sonia Nicholas, SelectScience's Clinical Editor spoke to Dr Ricardo Del Sol, Senior Lecturer at the College of Medicine, Institute of Life Science at Swansea University, UK, about using PointMan™ DNA Enrichment Kits and how working with EKF Diagnostics is leading to new advances in cancer diagnostics.

Working together

SN: Can you tell us about your collaboration with EKF and what are the objectives of the study?

RDS: The collaboration started in late 2013. At the time, a team of academics from the College of Medicine, Swansea University, had just secured funding from A4B (a Welsh Government funding scheme) to execute small research and development collaborative projects with industrial partners. EKF Molecular approached us with the idea of evaluating its PointMan™technology in the context of detecting low abundance DNA mutations associated with cancer in blood. We evaluated the PointMan kit using blood DNA from lung, skin and colorectal cancer samples obtained from the Wales Cancer Bank, and demonstrated that PointMan can enrich mutant alleles from DNA isolated from blood.

SN: How long have you been working on this study?

RDS: After the A4B-funded collaboration, we proposed to EKF Molecular the continuation of the studies with PointMan™, to determine its suitability to detect cancer-related mutations in blood from gynecological cancer patients, in particular endometrial and ovarian cancer. Currently, EKF Molecular is co-sponsoring a post-graduate student (funded by Nano and Micro Technologies in Healthcare) to conduct these studies.

SN: In addition to the PointMan™ kits, what other technology did you require to be able to analyze your specimens? Did you need any specialist systems or equipment?

RDS: Generic lab equipment and DNA isolation protocols are used to prepare samples prior to PointMan™ processing. In clinical samples where the cancer-related mutant DNA is at low abundance (in blood during early onset of disease or when patients are undergoing treatment) existing kits (real time PCR) are not always sufficiently sensitive. The PointMan™ platform is very effective at enriching mutant DNA isolated from tissue or blood. We have also realized that a DNA sequencing step is required to confirm the PointMan™ outputs. That is why we are currently optimizing a clinical sample processing pipeline, where PointMan™ is used to achieve the specific enrichment of mutant (or cancer related) DNA isolated from blood, followed by a next generation sequencing (NGS) step that provides both confirmation of the presence of the mutation and quantitative estimates of the abundance of the mutant DNA. Using PointMan™ in this context allows for the application of small-scale (and cheaper) NGS platforms, therefore making the pipeline affordable for small clinical labs.

Easy to use

SN: How easy is the PointMan™ kit to use? Do you see the technology being used in specialist clinical labs in the future or could any clinical lab with a molecular department utilize the technology?

RDS: It is very easy to use. The components are pre-mixed into reaction mixtures, so there is less room for human error. So far the results obtained are very reproducible. We are currently testing the kit and our sample processing pipeline with reference DNA samples containing known amounts of mutant DNA, and a subset of clinical samples. The results are very encouraging and demonstrate that Pointman™ is a very robust technology. There is certainly a need in the clinical diagnostics area for a technical platform that allows enrichment of low abundance mutant DNA from a complex mixture, and from blood in particular. If paired with a high coverage DNA sequencing platform, PointMan™ could become a must-have tool for clinical diagnostics, the evaluation of new anticancer drugs, and as a companion diagnostic tool to assess drug efficacy in patients.

SN: What results have you seen so far in your collaboration?

RDS: We have experienced a great interest by EKF Molecular to thoroughly validate the use of PointMan™ with a vast array of clinical samples. Also, the company is willing to embrace suggestions related to how the kit is best used, and how it can be improved. The company’s approach is very professional and honest in terms of determining the true value of the technology. The collaboration is producing very interesting results, and we hope to gather enough data to produce a scientific paper this year.

Revolutionizing cancer diagnostics

SN: What are the implications of these results for healthcare and cancer diagnostics?

RDS: At the moment cancer diagnostics relies heavily on traditional tissue biopsies to provide a clinical decision and guide therapeutic intervention. This approach requires invasive surgical procedures in most cases. Implementing technologies such as PointMan™ will permit non-invasive, early screening programs at population level for patients, in a personalized manner. The possibility of using blood as a source for DNA makes it a very attractive proposition for patients and healthcare providers who are otherwise reluctant to employ invasive interventions without compelling clinical reasons, usually correlated to advanced onset of the disease.

SN: What happens next? What are your future plans for this collaboration and the development of liquid biopsies?

RDS: We are currently applying for further funding, in partnership with EKF Molecular, to extend the studies to a wide range of clinical samples and to fully validate the PointMan™-NGS pipeline. A mid-term aim is to gather sufficient pilot data to justify the feasibility of large scale clinical trials assessing the value of the pipeline as a companion diagnostics tool for anticancer drug candidates.

SN: How long do you think it will be before we can expect to see such tests being used routinely in the clinical laboratory?

RDS: That is a question for the policy makers rather than the scientist! Implementing novel diagnostic tools requires extensive validation, dissemination within the scientific community and the general public, approval by regulatory bodies and finally the financial considerations associated to the introduction of new processes in healthcare. Currently, we can witness tremendous differences in the manner in which different health authorities choose how and when to implement already approved diagnostic procedures. It is likely that technology platforms such as the one we are developing with EKF Molecular will become first available in private clinical practice. In my personal opinion, we will have to wait for a bit longer before it arrives into publicly-funded healthcare.