Petros Christopouloso1, Jin Ye Yeo2
1Department of Medical Oncology, Thoraxklinik and National Center for Tumor Diseases (NCT), Heidelberg University Medical Center, Heidelberg, Germany; 2CCO Editorial Office, AME Publishing Company
Correspondence to: Jin Ye Yeo. CCO Editorial Office, AME Publishing Company. Email: editor@thecco.net
Expert introduction
Prof. Petros Christopoulos (Figure 1) is Professor of Medicine at Heidelberg University, Hematologist & Medical Oncologist in the National Center for Tumor Diseases (NCT) Heidelberg, Head of Scientific Coordination for the Thoracic Oncology Program in the Thoraxklinik, and Principal Investigator in the Translational Lung Research Center Heidelberg, member of the German Center for Lung Research (DZL). He is responsible for several clinical and translational research studies, as well as for the weekly thoracic molecular tumor board and subsequent treatment using novel compounds off-label or within expanded access. After studying medicine in the University of Athens, Greece, he completed his training in Internal Medicine, Emergency Medicine, Hematology, Hematopoietic Cell Transplantation, Medical Oncology, Genetic Counseling, and Palliative Care in the University Hospitals of Freiburg and Würzburg in Germany. The major focus of his research lies in the systematic integration of clinical with genetic, pathologic, immunologic, and radiologic data to refine patient stratification, improve disease monitoring and identify novel therapeutic targets, which are subsequently translated into advanced preclinical models and investigator-initiated phase 2 trials.
Figure 1 Prof. Petros Christopoulos
Interview
CCO: What inspired you to venture into the field of thoracic oncology, and subsequently focus your research on non-small cell lung cancer (NSCLC)?
Prof. Christopoulos: Two key reasons were the exceptional progress during the past decade in the treatment of NSCLC, regarding both molecularly-targeted drugs and immunotherapy, as well as the prospect to combine clinical with scientific work. After finishing my specialist training in 2011, I initially worked mainly as a hematologist, including the Multiple Myeloma and allogeneic hematopoietic cell transplantation (HCT) services in the University Hospitals of Freiburg and Würzburg, which was a very challenging and rewarding experience. However, I soon realized that the potential in Thoracic Oncology, particularly in Heidelberg, was much higher.
CCO: Could you provide a brief overview on the recent publications in immunotherapy for NSCLC? Are there any findings that stood out to you?
Prof. Christopoulos: During the last years, PD-(L)1 inhibitors, alone or in combination with chemotherapy, were established as the standard of care for advanced lung cancer and their use is now gradually also spreading to the earlier stages. Engineered antibodies, like antibody-drug conjugates (ADCs), multispecific constructs and T-cell engagers, comprise the next wave of immunotherapy, which is currently rising fast, but ultimately limited by the availability of suitable tumor-specific surface antigens. Therapeutics targeting intracellular neoantigens, for example T-cell receptor (TCR)-mimic antibodies and transgenic TCR-T cells, have recently demonstrated even greater potential and could radically transform the field, but their broader availability will take several more years.
CCO: Your multidisciplinary approach in integrating clinical, genetic, pathologic, immunologic, and radiologic data is at the forefront of personalized cancer treatment. What inspired you to adopt this holistic approach, and how has it transformed your research in thoracic oncology?
Prof. Christopoulos: It started out of the desire to leverage all available resources in order to understand human disease better. In the earliest projects, we combined deep clinical annotation with state-of-the-art matched DNA/RNA next-generation sequencing (NGS), which revealed the adverse clinical phenotype associated with the shorter EML4-ALK variant 3 and led us to propose the first molecular risk stratification for ALK+ NSCLC, with single and double positive tumors based on V3 and TP53 status, already back in 2018. In this regard, it was also certainly helpful that I had already been familiar with similar concepts from my previous work in Hematology. More recently, we have been dissecting the biology of high-risk ALK+ disease using preclinical models and also prospectively exploring clinical implications, like the need for closer, ctDNA-based monitoring or more potent upfront therapies for patients with more aggressive tumors, within a phase 2 trial. Besides, we are expanding our approach to include radiologic and immunologic data and address further NSCLC subsets, like tumors receiving immunotherapy or harboring other oncogenic drivers, like EGFR exon20 insertions and MET exon14 skipping.
CCO: As the Head of Scientific Coordination for the Thoracic Oncology Program, how do you ensure that the latest scientific insights are effectively translated into patient care, particularly in complex cases involving novel compounds?
Prof. Christopoulos: Patients failing standard therapies are subjected to extended molecular profiling with combined DNA/RNA NGS for 500+ genes or whole exome sequencing (WES)/whole transcriptome sequencing (WTS), and subsequently discussed in our weekly Thoracic Molecular Tumor Board in order to maximize therapeutic options. Novel compounds without regulatory approval are available through clinical trials, expanded access programs, or simply off-label after obtaining consent from health authorities, if already available in the market for other indications.
CCO: The weekly thoracic molecular tumor board you oversee is pivotal in guiding treatment decisions. Could you share an example of how this interdisciplinary collaboration has led to a breakthrough in patient management or treatment strategy?
Prof. Christopoulos: The Thoracic Molecular Tumor Board report plays a key role in translating molecular results into therapeutic opportunities. The resulting report is an essential supporting document for applications to use drugs off-label for patients with potentially sensitive alterations, like HER2amp with T-DXd, BRAF p.K601 or class II mutations with BRAF/MEK inhibitors, secondary BRAF fusions with trametinib, secondary MYC amplification with dasatinib etc. With > 150 such cases to date, we have seen many responses lasting for several weeks, which we document within the Center for Personalized Medicine (ZPM) Heidelberg to guide future therapeutic decisions and simplify drug access for subsequent patients.
CCO: Moving forward, how do you envision the future of personalized treatment in lung cancer evolving?
Prof. Christopoulos: Both targeted drugs and immunotherapies will become increasingly tailored to each patient’s particular molecular profile as assessed by large NGS panels in the next few years. Remaining oncogenic drivers will also gradually become actionable via the use of novel kinase inhibitors, while custom neoantigen-directed therapeutics, in particular armored TCR-T cells, will be used to target mutations of tumor suppressors and other clonal alterations in a personalized manner. Minimally invasive monitoring using serial liquid biopsies will be used to track tumor evolution and remission status in order to adapt management accordingly.
CCO: How has your experience been as an Editorial Board Member of CCO?
Prof. Christopoulos: Looking back at my first full year as an Editorial Board Member of CCO, my experience has been very positive. Communication and collaboration with the CCO staff were always prompt and smooth at all times, while I always retained the flexibility to adjust any tasks according to other obligations. While preparing a Review Article for the CCO a few months ago, I could first-hand appreciate the high-quality standards, meticulous attention to detail, and excellent support of the Editorial Office.
CCO: As an Editorial Board Member, what are your expectations for CCO?
Prof. Christopoulos: I expect that the CCO will continue to cover all important developments in Oncology and become an important bridge between the dynamic Chinese medical community and the rest of the world. China has made huge progress in basic and translational cancer science during the last few years, which is reflected in many novel drugs and cutting-edge clinical trials. These achievements have sparked great interest globally, and could also further benefit from closer interaction with specialists from other countries.