Analysis of plasma, platelets and urine nucleic acids: the value of liquid biopsy to improve diagnosis, follow-up and monitoring of treatment response of lung cancer and pancreatic cancer patients.

In order to provide cancer patients with personalized treatment, molecular understanding of the tumor is indispensable. Therefore, tumor biopsies are needed. However, tissue biopsies might put the patient at risk and are encumbered by heterogeneity and suboptimal tissue acquisition. On the other hand, circulating tumor DNA (ctDNA) and RNA (ctRNA) in liquid biopsies are not only of interest during the initial work-up of a cancer patient, but also because of this approach allows monitoring of the disease during treatment, including the detection of acquired resistance, which can enable a fast switch to an alternative therapy.In this project we will evaluate the use of plasma, platelets and urine as liquid biopsy in the setting of real-time disease monitoring in a patient-friendly way. We will concentrate specifically on two tumor types with poor prognosis, i.e. non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC). Investigating urine as non-invasive sampling method and the value of liquid biopsies to monitor response to immunotherapy are two major innovative goals of this project.As the first objective, we will investigate the correlation between blood, urine and tumor tissue of NSCLC patients for the detection of targetable mutations. For the first time, real-time follow-up will be established by screening the ctDNA and ctRNA from blood and urine samples of not only EGFR mutated NSCLC patients, but also ALK- and ROS1 translocated patients during tyrosine kinase inhibitor (TKI) therapy for known and novel resistance mechanisms.Furthermore, the prognostic and predictive value of the quantification of mutated ctDNA and ctRNA in blood and urine will be examined. As the second objective, KRAS mutated NSCLC patients as a non-targetable mutation will be included in order to correlate the mutational status of blood, urine and tumor tissue. The innovative aspect is that both patients undergoing surgery with curative intent and patients undergoing chemotherapy will be included. Furthermore, a proof-of-concept study with blood and urine samples from PDAC patients before and during neoadjuvant therapy and pre- and post-surgery will be performed to assess the necessity and success of the therapy. The third objective is to develop liquid biopsy-based assays inn order to monitor the immune system and tumor load during immune therapy, which is now hampered by the concept of pseudoprogression and the lack of reliable biomarkers. At the moment there are no reliable data on the evolution of tumor necrosis during immune therapy. We will evaluate if monitoring immune makers and proliferation via liquid biopsy can predict which patients benefit of this costly therapy.To conclude, the results of this study will boost implementation of liquid biopsies (plasma and/or urine) in routine clinical care to facilitate personalized treatment of cancer patients.

Keywords:PANCREAS

Disciplines:Morphological sciences, Oncology