Pancreatic cancer is a tumoral disease with one of the bleakest prognoses. And despite the various advances in oncology over the previous 30 years, not one has been able to significantly improve its treatment. But Richard Tomasini is looking to change that: he is studying a marker which, when measured in the blood, could improve the efficacy of pancreatic tumor surgery…
You have devoted your research to pancreatic cancer for almost 20 years now. Why is this disease so difficult to fight?
In reality, pancreatic cancers present numerous particularities: whereas the majority of other cancerous tumors are made up of abnormal cells, pancreatic tumors may comprise up to 90% healthy cells. These tumors are also surrounded by thick nerve fibers that form progressively and enable certain cancerous cells to migrate easily to form remote metastases. In reality, we observe that there are many interactions between the tumor and its microenvironment and that some of the messengers emitted by the surrounding cells – known as stromal cells – can render the tumor very aggressive. Whereas experimental treatments over the past 30 years have exclusively targeted the cancer cells, it appears clear today that the stromal cells must also be targeted to the same extent in order to fight the disease effectively. But a final difficulty lies in the fact that not all stromal cells have protumor activity. So, we must be capable of targeting those with protumor activity while preserving those involved in the anti-tumor immune response.
The PAP biomarker is the subject of a study for which you have recently obtained a European Research Council (ERC) Proof of Concept (POC) Grant. Is it one of these key mediators?
Yes, PAP is a protein which is produced by the stromal cells to launch an anti-inflammatory response. However, it can be hijacked by the tumor cells in order to increase their development and their ability to penetrate nerve fibers. It is a protein that we identified during a previous project, for which I obtained ERC funding in 2011. As part of the POC Grant, our objective is currently to evaluate whether measuring PAP levels in the blood can help improve the selection of patients for whom surgery would be beneficial. Until now, only tumor size and clinical presentation of the disease have enabled doctors to decide whether or not it is worth operating. Indeed, conventionally, a large tumor is linked to lower chances of survival. However, we observed that while some pancreatic cancers are small in size they are very aggressive, which reduces the chances of successful surgery, whereas other larger tumors have less risk of recurrence or metastasis. We think that PAP measurement can be used as a biomarker in this context: we were able to establish a threshold level that can be used to determine whether or not it is useful to operate, with the best chances of survival. As such, taking tumor biology into account would help orient surgical decisions and therefore improve patient outcomes.
What will you be able to achieve with this funding?
The 150,000 euros of the POC Grant will allow us to recruit a clinical research assistant who will contact the hospitals which treat the disease and which have blood biobanks. We will then be able to retrospectively establish whether the patients with the lowest PAP levels are indeed those who had the best mean survival after surgery. Funds to finance translational research are thin on the ground and, in that, the grant is a unique opportunity to transform a biological discovery into clinical progress which, in addition, concerns the treatment of a disease in which therapeutic innovation remains rare.