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Project
Interdisciplinary Network in Fundamental and Medical Research on Lung and Pancreatic Cancer [NITROGEN] (IRP9_b)
Non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) are among the deadliest cancers with limited therapeutic options resulting in 5-year overall survival rates of less than 20% and 10%, respectively. Moreover, the incidence of PDAC is rising.
This proposal aims, therefore, to identify and (pre-)clinically validate a set of molecular targets as drivers of cancer phenotypes that could be used for mono- or combination therapies in lung and/or pancreatic cancer. This will be underpinned by exploring new targeted therapies via the chemical synthesis of lead compounds – through a combination of medicinal chemistry and de novo-based approaches – able to inhibit/modulate these newly identified molecular targets. Studies on the de-ubiquitinase USP13 and the kinase STYK1 for NSCLC (outcome of 1st term IRP9) and the recently identified novel target ROBO1 for PDAC are ongoing. In addition, clinical samples of NSCLC and PDAC will be subjected to extensive molecular profiling that can illuminate additional molecular targets to be characterized by the consortium. Optimized ligands will be preclinically validated using state-of-the-art experimental models before bringing them forward for clinical testing.
This project will leverage the identification of potentially druggable targets with the subsequent design of innovative therapeutic agents that will underpin biomarker-driven precision medicine in two of the deadliest cancers. The overarching goal of the program is to improve the current therapies and outcome (survival and quality of life) of patients diagnosed with these cancer types.
This proposal aims, therefore, to identify and (pre-)clinically validate a set of molecular targets as drivers of cancer phenotypes that could be used for mono- or combination therapies in lung and/or pancreatic cancer. This will be underpinned by exploring new targeted therapies via the chemical synthesis of lead compounds – through a combination of medicinal chemistry and de novo-based approaches – able to inhibit/modulate these newly identified molecular targets. Studies on the de-ubiquitinase USP13 and the kinase STYK1 for NSCLC (outcome of 1st term IRP9) and the recently identified novel target ROBO1 for PDAC are ongoing. In addition, clinical samples of NSCLC and PDAC will be subjected to extensive molecular profiling that can illuminate additional molecular targets to be characterized by the consortium. Optimized ligands will be preclinically validated using state-of-the-art experimental models before bringing them forward for clinical testing.
This project will leverage the identification of potentially druggable targets with the subsequent design of innovative therapeutic agents that will underpin biomarker-driven precision medicine in two of the deadliest cancers. The overarching goal of the program is to improve the current therapies and outcome (survival and quality of life) of patients diagnosed with these cancer types.
Date:1 Jul 2021 → Today
Keywords:Pancreatic Cancer, Lung Cancer
Disciplines:Philosophy of medical and biomedical sciences