Research Jeroen Hendriks

Abstract

Lung transplantation is the ultimate option for selected patients with an end-stage pulmonary disease. However, there are many complications that limit the success of lung transplantation. Many pathophysiological mechanisms remain unknown. Within this project, the role of the vasculature will be further unraveled in the different important post-transplant complications (i.e. ischemia reperfusion injury, acute rejection and chronic lung allograft dysfunction). By leveraging an innovative murine model of lung transplantation and state-of-the-art techniques such as bulk transcriptome, microCT and immunostainings, we want to investigate the role of the vasculature in the pathophysiologic mechanism of these complications. These findings will be further validated in a human setting as well, by utilizing well-characterized human samples. The last aim of this project is also to find a way to influence the vascular changes by using a therapeutic intervention in the murine model pre- and post lung transplant. These findings will be crucial to better understand the importance of vascular changes in post-transplant complications and finally also to better treat or prevent these. This will lead to a better survival of this group of very vulnerable patients.

Researcher(s)

• Promoter: Hendriks Jeroen
• Fellow: Coppens Axelle

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

The research activities of the consortium IPPON (Integrated Personalized & Precision Oncology Network) are at the forefront of integrated personalized cancer medicine, with emphasis on 1) developing novel and more effective therapeutic strategies; 2) an improved detection and understanding of mechanisms driving therapeutic resistance; and 3) identifying and validating biomarkers for early detection and personalized therapy, in different cancers in need for improved therapeutic outcomes. In this way, we aim to deliver the right treatment to the right cancer patient at the right time. Novel and emerging anticancer strategies that we investigate include - but are not limited to - locoregional perfusion, targeted therapy, immunotherapy, cold atmospheric plasma therapy as well as novel combination therapies. We are convinced that the interdisciplinary collaboration between basic, translational and clinical researchers, catalyzed through this consortium, will enable us to tackle burning research questions and clinical unmet needs to advance the field of personalized cancer medicine. The members of our consortium bring together unrivaled access to biobank patient samples and to a dedicated clinical phase I/II oncological unit with a unique and complementary set of methods and skills covering the entire spectrum of molecular techniques, 2D and 3D cellular assays (in vitro and ex vivo), small- and large animal studies and clinical studies. IPPON gathers experts with an excellent research track record in fundamental, translational and clinical oncology; surgical techniques; targeted therapy; immunotherapy; (epi)genomics; (epi)transcriptomics; proteomics; imaging; liquid biopsies; pathology and clinical studies.

Researcher(s)

• Promoter: Peeters Marc
• Co-promoter: Dewilde Sylvia
• Co-promoter: Hendriks Jeroen
• Co-promoter: Lardon Filip
• Co-promoter: Pauwels Patrick
• Co-promoter: Smits Evelien
• Co-promoter: Van Dam Peter
• Co-promoter: Vanden Berghe Wim
• Co-promoter: Van den Wyngaert Tim

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Patients with advanced lung cancer or lung metastases are treated with chemotherapy as single modality or within a multimodality regimen such as immunotherapy. Although these patients may be eligible for treatment with intravenous (IV) chemotherapy and/or immunotherapy, systemic side effects have a significant impact on the quality of life and may result in early termination of treatment in case of severe side effects. This is especially true for chemotherapy, but it is even more true in the era of immunotherapy, when this new promising therapy is combined with chemotherapy. Our group has demonstrated that isolated lung perfusion (ILuP) is able to deliver high doses of chemotherapy to the lung by using a closed lung bypass circuit, with no systemic exposure. When combined with selective pulmonary artery perfusion (SPAP), it enables the delivery of systemic therapy to the lung, without the need to perform a major surgical procedure. When SPAP in our laboratory was combined with blood flow occlusion (BFO) to delay the washout of chemotherapy in the lung, it resulted in even higher lung doses compared to SPAP only, but with less systemic exposure and no systemic side effects. In this project, we want to perform the necessary translational experiments and gather substantial preclinical evidence to initiate a first of its kind human phase 1 trial to investigate the distribution of chemotherapy using selective pulmonary artery perfusion with blood flow occlusion. In WP1, we will perform porcine experiments to assess technical feasibility and to investigate the optimal protocol to deliver chemotherapy, assessed by local drug delivery and local side effects. In WP2, we aim to take the first step towards human validation. Using patient-derived 3D printed models, we will assess the human-specific challenges that need to be overcome to further implement this technique in patients. As a last step towards human validation, WP3 will employ human excised specimens to re-assess the technical aspects of this technique, as well as to confirm regional toxicity induced by local chemotherapy treatment. Ultimately, we believe that these experiments provide indispensable information which will lead to the introduction of this technology into a phase I clinical trial and finally as routine care so that the benefits of repeated application and reduced systemic side-effects can be of significant benefit for a large population of patients with (advanced) NSCLC.

Researcher(s)

• Promoter: Hendriks Jeroen

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project