An interview with Ana Vivancos, Principal Investigator of VHIO´s Cancer Genomics Group
“We are one of the few groups in Europe to provide a pre-screening program of mutations in patients who are candidates for phase I clinical trials”
What is VHIO´s Cancer Genomics Group´s main focus of activity?
Our Cancer Genomics Group does not serve as a common research laboratory; rather it acts as both a core technology and translational research unit at the heart of VHIO´s research activities. While we pursue, and implement our independent research projects, we are also dedicated to performing core facility analyses and services that we are continuously and rapidly developing. Concerning the latter, our most important project is pre-screening for mutations in patients who are candidates for Phase I clinical trials carried out at VHIO. We are one of the few groups in Europe to do so. Currently, at an equivalent level to us, there are only around 4 other European cancer research centres doing this. Such pre-screening programs are more common in the US, although they are all located at centers renowned for excellence in Phase I trials.
How does your group differ from other laboratories that determine mutations in oncology practice?
In standard oncological practice, the mutational state of a gene is studied within the context of a specific tumour type and when there is an existing, approved therapeutic strategy for the gene under study such as EGFR in lung and KRAS in colorectal cancer. We do not limit our scope to one gene in a particular tumor type. Using a mutation panel, we study 273 mutations in 23 oncogenes at the same time, in all tumor types. We screen for known mutations as well as those for which there are new targeted drugs currently in clinical drug development. These target against relevant cell activity in cancer, such as the PI3K inhibitor, a protein that plays an important role in tumour growth in many cancers.
What is the advantage of studying 273 mutations over only one?
By broadening the range of mutations under study we find more mutated samples, opening up more avenues when it comes to patient stratification. Further, since we have such a wide panel, we sometimes find mutations that are usually detected in one kind of tumour in a totally different one, which would never have been explored otherwise. One case exemplifying this was a mutation in a gene typically implicated in breast cancer that we found in a patient with lung cancer. Thanks to this discovery, the patient received treatment that is normally administered to breast cancer patients. Such incidental, yet crucial findings are not reported very often, possibly in less than 2% of cases, but they can and do occur.
Which patients are candidates for your programme?
All patients who have exhausted all clinical treatment possibilities and are eligible for enrolment in a Phase I clinical trial. Results from our pre-screening inform us about the mutational state of the oncogenes under study in the patient´s tumor. Our programme currently deals with around 1,000 patients per year.
Which techniques are you currently adopting for pre-screening? What does the future hold?
We currently use the SEQUENOM platform to search for oncogenes but we aim to migrate patients to ultra-sequencing. This will enable us to detect 5 times more mutations with the same panel. Another advantage of ultra-sequencing is that it will be easier to enlarge the panel and thus start to study tumour suppressors as well.
What other alterations can be identified with the panels you design?
There are many types of alterations implicated in cancer that promote uncontrolled cell proliferation or reduce immune system response, among other strategies. Currently, for instance, we are using the nCounter NanoString platform in collaboration with Aleix Prat, Principal Investigator of VHIO´s Translational Genomics Group, to develop a panel capable of detecting certain gene fusions in colorectal cancer.
What is the role of gene fusions in onco-processes in colorectal cancer?
The presence of certain gene fusions can increase the presence of a given protein (e.g. ALK in lung tumors), or the appearance of new functions in a tumour resulting from the fusion of two normal protein fragments that, together, generate a new protein with new activity. These fusion proteins do not appear in normal cells, but spur tumor growth.
Earlier you alluded to your group´s translational research. Can you be more specific?
Yes, we are in fact one of VHIO´s most translational laboratories collaborating with many preclinical and clinical research groups. In addition, we are involved in the steps that follow the identification of mutations, helping our researchers to prioritize those mutations that could be the most important in cancer development. At VHIO, it´s all about teamwork. We promote and develop dynamic, proactive collaboration between our groups and programs.
Could the pre-screening programmes pioneered and developed by your laboratory at regional and national level, become common practice in the treatment of cancer?
Initiatives are starting to be developed to implement this pre-screening programme in earlier phases. One such project, involving a number of Catalan hospitals, will focus on creating a center for the molecular study of recently diagnosed patients and carry out a pre-screening test in colorectal cancer. Funding is currently being sought for this initiative. Additionally, a molecular screening platform has been established by the cooperative research group SOLTI, with its primary node in our Institute. Its main objective will be to obtain the mutational profiles of metastatic breast cancer patients.
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For more information surrounding VHIO´s Cancer Genomics Group, its services and research activities please contact: Amanda Wren, Email: awren@vhio.net, Tel.:+34 695207886.
