Project: ‘PLATELET-POWERED COMPANION DIAGNOSTICS FOR THERAPY MONITORING OF LUNG CANCER PATIENTS (PLATO)
Lung cancer continuous to be the leading cause of cancer-related death in both men and women and is a major public health problem. Each year 1.35 million people are diagnosed with lung cancer, compromising 12.4% of all new cancer cases. _x000D__x000D_Depending on the patient’s medical status and stage of disease, systemic cytotoxic chemotherapy, surgery, and/or targeted therapies are the COstay for treatment for NSCLC patients [1]. The discovery of various molecular alterations that underlie lung cancer has opened-up a new era in the development of specifically targeted therapies employing specific mutation inhibitors. These oncogenes include amongst others EGFR, KRAS, and ALK. Identifying mutations in oncogenes associated with NSCLC can help to determine which patients are more likely to benefit from targeted therapy. Patients with activating EGFR mutations are generally responsive to EGFR-directed kinase inhibitors, whereas those with ALK mutations (translocations) are candidates for treatment with the ALK inhibitor crizotinib. Patient stratification for EGFR, KRAS, and ALK mutations is now common practice among oncologists and the introduction has been an important milestone for more individualised treatment._x000D__x000D_Monitoring the mutational status of NSCLC patients is of crucial importance to tailor targeted therapy [2] [3]. The mutational status of NSCLC patients is dynamic and changes in due course of the disease. NSCLC patients, for example, with only EGFR mutations at baseline may also present with an ALK mutation. With ALK mutations, patients may not have the best benefit from initial anti-EGFR therapy anymore and their treatment may need adaptation to anti-ALK therapy. Information on the dynamic mutational status is highly needed in order to monitor and/or adapt treatment regimes. Longitudinal monitoring of the mutational status is needed to improve personalised NSCLC treatment, providing each patient with tailored targeted therapy._x000D__x000D_Limited access to tumour biopsies constitutes a major shortcoming in longitudinal molecular monitoring and targeted treatment of NSCLC patients. NSCLC patients frequently need to undergo bronchoscopy and/or surgical procedures in order to obtain highly quality tumour tissue that can be used to assess the mutational status. Both methods are invasive, costly, and not suitable for longitudinal monitoring. Currently, circulating free DNA in plasma is being evaluated as a biosource for mutational monitoring. However, such plasma assays have thus far not resulted in robust diagnostics tests, possibly due to the exposure of the circulating free DNA to degradative enzymes highly present in the blood, resulting in low quality nucleic acids for mutational analysis. Therefore, new blood-based assays providing high quality nucleic acids for longitudinal monitoring of the mutational status in NSCLC patients are highly needed._x000D__x000D_TDx discovered an entirely new biological source for obtaining high-quality tumour-derived nucleic acids. We have found that thrombocytes (blood platelets), which are used for decades in clinical practice, allow for isolation and identification of tumour-derived (mutant) RNAs. In a proof of concept study (see addendum) we demonstrated that platelets have the ability to internalize tumour-derived RNA of high-quality [4], see figure 1. We identified high quality KRAS, EGFR, and ALK mutant RNAs in blood platelets of cancer patients. This intriguing finding meets current requirements for longitudinal NSCLC diagnostics as it is non-invasive, easy-to-use, and therefore allows for monitoring the mutational status without the need for subsequent biopsies. Platelet measurements are thereby part of the daily routine of clinicians and analysts. _x000D__x000D_The Eurostars PLATO project aims to further validate our platform technology on large patient cohorts and to develop a companion diagnostic product and/or service for NSCLC diagnostics. The project is a strong enabler for starting commercial exploitation as it provides the long-awaited results which will allow us to close a strategic Pship with diagnostics companies, but also big pharma companies that need accurate companion diagnostics for new targeted therapies based on EGFR, KRAS, and ALK mutations. PLATO is a strong Pship between thromboDx (TDx), VU University Medical Center (VUmc), and Umea University (UMEA). Next to TDx that exclusively owns the patented blood platelet-powered diagnostics technology, specialised pulmonary oncologists at the VUmc will participate and PLATO will synergise with a recently stared phase IV clinical trial that studies the effectiveness of gefitinib in advanced NSCLC patients, which provides the perfect opportunity to validate the technology via longitudinal monitoring of the mutational status. The Nilsson group at UMEA is one of the most advanced RNASeq infrastructures. Their expertise is needed to select the most appropriate RNAseq read-out for our platelet-powered diagnostics platform.
|
Acronym
|
PLATO
(Reference Number: 8626)
|
|
Duration
|
01/10/2013 - 31/12/2015
|
|
Project Topic
|
PLATO aims to develop a non-invasive molecular diagnostic test based on our patented blood platelet technology to monitor the dynamic mutational status of NSCLC patients for personalised medicine.
|
|
Network
|
Eurostars
|
|
Call
|
Eurostars Cut-Off 10
|
Project partner
