One of the main criteria in the evaluation process is a high potential for the project to lead to an innovative clinical application. Another important aspect is to strengthen collaborations among researchers at Amsterdam UMC. This year, nine promising projects will receive funding. Cancer Center Amsterdam - Amsterdam UMC congratulates all awarded researchers.
Dr. Daniela E. Oprea-Lager – ‘Artificial intelligence-based response prediction on diagnostic PSMA PET-CT as a tool for a personalized treatment approach in patients with metastatic hormone-sensitive prostate cancer’
There is a need to tailor treatments for patients with prostate cancer to improve their oncological outcome. The goal of Dr. Oprea-Lager and her group is to extract a large number of characteristics from PET scans of metastatic prostate cancer using radiomics, and then to apply machine learning in order to identify high-risk tumor characteristics and predict treatment outcome. Also, deep learning algorithms will be developed for the same purpose. This non-invasive method could improve the prediction of treatment responses and the prognosis of the disease.
Dr. Rieneke van de Ven – ‘The GARP/TGF-β axis: a critical immune regulatory pathway in head and neck cancer?’
Most head and neck tumors do not show a lasting response to immunotherapy. The hypothesis of Dr. Van de Ven is that transforming growth factor-beta (TGF-β), a signaling molecule that plays a crucial role in suppressing immune responses and promoting tumor growth, is excreted via tumor cell vesicles into the microenvironment,. The proposed study aims to elucidate how released TGF-β is activated and how GARP receptors in the microenvironment support this activation. Next the study will assess if the GARP/TGF-beta axis limits anti-tumor immune responses. The findings from this project may result in the development of more effective immunotherapy for head and neck tumors.
Dr. Caitrin Crudden – ‘Genome-wide CRISPR screen for novel modulators of cancer exosome release’
There are strong indications that aggressive tumor cells produce small vesicles (exosomes) that manipulate their environment to stimulate tumor growth and metastasis. Dr. Crudden has developed methods to measure the production of these exosomes by making them fluorescent, and now aims to use CRISPR/Cas genome-wide screens to investigate which genes play a role in their production. The results could lead to new therapeutic strategies to inhibit exosome production by aggressive cancer cells.
Dr. Cristina A. Gómez Martín – ‘Accurate isomiR detection for non-invasive PDAC diagnostics’
In patients with pancreatic cancer, tumors often go unnoticed for a long time resulting in a poor prognosis. To detect pancreatic cancer at an early stage and in a non-invasive way, Dr. Gómez Martín is aiming to isolate tumor-derived vesicles (exosomes) from blood and urine to identify microRNAs and isomiRs that indicate the presence of pancreatic cancer. In order to make this method reliable and reproducible, different pattern recognition techniques based on statistics and Artificial Intelligence will be tested.
Dr. Niels Verburg – ‘Multimodal image-guided resection of glioblastoma’
For glioblastoma brain cancer surgery, imaging by magnetic resonance (MRI) is not capable of revealing the entire tumor, which prevents the removal of all malignant tissue. A combination of positron emission tomography (PET) and MRI reveals more of the tumor. The aim of this project is to develop the technique of surgical removal of glioblastoma using the combination of PET and MRI. The second goal is to determine how accurately a new MRI technique, amide proton transfer-chemical exchange saturation transfer (APT-CEST), can image glioblastomas. Altogether, improvements in glioblastoma imaging technologies are aimed to develop safe and effective surgical procedures to improve patient survival as well as to extent the period of higher quality of life.
Dr. Rodrigo Leite de Oliveira – ‘Identifying stromal regulators with therapeutic potential in pancreatic cancer’
There are only limited therapeutic options for patients with Pancreatic Ductal Adenocarcinoma (PDAC) that are notoriously resistant to the current standard of care. Our limited understanding of PDAC inhibits the development of effective therapies against this aggressive tumor. PDACs are characteristically rich in stroma, non-cancerous supporting tissue. This stroma contains different subtypes of cancer-associated fibroblasts (CAFs) whose exact role is unclear - these cells have shown both tumor-promoting and tumor-inhibiting characteristics. In this project, regulators of CAF heterogeneity and their impact on PDAC biology will be elucidated by performing functional genome-wide CRISPR screens. The project findings may identify potential diagnostic or therapeutic biomarkers that also have relevance to other stroma-rich solid cancer types.
Dr. Alan Gerber – ‘Precision targeting of aminoacyl-tRNA-synthetases in cancer’
Tumor growth depends on the ability of cancer cells to produce a large number of proteins using tRNA molecules that carry protein building blocks. These protein building blocks – the amino acids - are attached to tRNAs by aminoacyl-tRNA-synthetases (ARS enzymes). Specific ARS enzymes are potential therapeutic targets as tumor cells often disproportionately overexpress particular tRNAs. Using glioblastoma brain tumor cells as a model, Dr. Gerber and his group will apply CRISPR interference to study the functional roles of ARS enzymes and determine the toxicity of specific ARS inhibitors in cancerous and normal cells as a first step towards potential therapy development.
Dr. Suzanne S. Gisbertz – ‘Optimizing lymph node staging in esophageal cancer with USPIO-enhanced MRI’
Pre-operative imaging technologies are crucial for delineating the tumor margins for resection and establishing the extend of lymph node involvement in locoregional metastatic disease. Current imaging techniques fall short of determining these characteristics in esophageal cancer, which is reflected in a poor clinical staging of affected patients: up to 43% are upstaged and 25% are downstaged. This makes patient tailored treatment (individualization of radiotherapy fields and surgery) not possible, and part of patients are over-or undertreated, which can lead to increased morbidity or decreased survival. In addition, some patients have a complete pathological response to neoadjuvante therapy, but this cannot be reliably determined yet. This project will focus on the optimization of 3 T MRI with the use of USPIO-contrast (ultra-small superparamagnetic iron oxide nanoparticles) to image suspected lymph nodes. USPIO enhanced MRI will be compared with current imaging. In addition, the response to neoadjuvante therapy will be evaluated.
Dr. Daniël Lionarons – ‘The role of serum response factor (SRF) as a driver of chemoresistance in colorectal cancer’
There is an urgent need to understand therapy resistance in colorectal cancer and to develop new treatments to counteract this. Dr. Lionarons and his colleagues propose that chemoresistance of CMS4 colon cancer, the most chemo-resistant subtype of colon cancer, can be counteracted by inhibition of transcription factor SRF. They aim to investigate in which cell compartment of the tumor stroma SRF is active by means of single-cell RNA sequencing and immunofluorescence microscopy. Furthermore, the effect of SRF inhibitors will be studied in cell culture and mouse tumor models as a first step towards clinical translation.
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Text adaptations by Esméé Joosten