As a cardiologist, you diagnose and treat people with various heart conditions. At the same time, you have also been working for several years on cancer therapies based on the use of ICIs. What is the relationship between cancer therapy and heart disease?
Rassaf: Cancer patients treated with ICI often have to deal with more or less severe adverse reactions that can affect various organs, not infrequently the heart. We want to understand the exact cause of this.
How often do these adverse reactions occur?
Rassaf: In the first year of their treatment, up to ten percent of cancer patients exhibit severe immune-mediated adverse reactions.
In the 2021 paper published in the European Heart Journal, you and your co-authors were able to show that heart damage can be avoided if tumour necrosis factor-α, or TNF-α, is inhibited beforehand. How did you come to explore this connection?
Rassaf: In previous studies, there was evidence of TNF-α involvement in the intestinal tract and experiments that yielded similar results. This is the approach we have taken with hearts over the past four years. Our goal continues to be, first and foremost, to develop a therapeutic approach with which we can both treat the cancer effectively, with new drugs for example, and exclude the negative sides of the treatment such as ad-verse reactions and consequential damage. The aim is to prolong the lives of cancer patients without causing additional damage through immunotherapy.
Michel L, Helfrich I, Hendgen-Cotta UB, Mincu R-I, Korste S, Mrotzek SM, Spomer A, Odersky A, Rischpler C, Herrmann K, Umutlu L, Coman C, Ahrends R, Sickmann A, Löffek S, Livingstone E, Ugurel S, Zimmer L, Gunzer M, Schadendorf D, Totzeck M, Rassaf T. Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy. European Heart Journal, Bd. 43, Nr. 4, S. 316–329. https://doi.org/10.1093/eurheartj/ehab430
Do you have other »candidate« drugs in mind besides TNF to prevent damage to the heart or other organs during tumour therapy?
Rassaf: Yes, there are already others under consideration. We want to conduct new studies on them in the preclinical area, for example in animal models or cell cultures, during 2022, so the results are naturally not yet available. We are working closely with ISAS on this research. The institute’s multi-omics analyses provide us with important biochemical and physiological data, for example for understanding adverse reactions. In the coming years, we would like to devote ourselves to the question of exactly how immunotherapies work.
Are there any other research partners in this regard?
Rassaf: Yes, in addition to ISAS, we cooperate here on site with the Tumour Clinic and Nuclear Medicine or Radiology. We also have an exchange with Charité – Universitätsmedizin Berlin and the Cologne University Hospital.
What other projects are you currently researching?
Rassaf: We currently have two studies underway. The first addresses the question of how to prolong the lives of cancer patients with cardiac damage. The second study concerns exercise, or more specifically, exercise as a possible means of preventing premature heart damage.
How do you envisage your scientific work in the next few years?
Rassaf: We advertised two joint professorships in cooperation with ISAS in 2021. Both could be titled »Individualisation of Medicine«. One of these professorships is located entirely at ISAS in Dortmund. The task there will be to examine samples from patients in detail using multi-omics analyses in order to obtain new, detailed information on the metabolism of individual patients. The other professorship at the University Hospital will build on this. It should lead to the development of new treatment procedures in cardiology. Our common goal is ultimately a tailor-made therapy, individually adapted to each patient.
PROF DR TIENUSH RASSAF
has been Director of the Cardiology and Angiology Clinic at the West German Heart and Vascular Centre (University of Duisburg-Essen) since 2015. The range of treatments offered by his clinic includes all areas of cardiovascular medicine, including all therapies for coronary heart disease, cardiac arrhythmias, valvular heart disease, heart failure, aortic diseases and congenital heart defects, as well as emergency and intensive care medicine. Rassaf is one of the initiators of the nationwide Oncological Cardiology research group, which was established in 2018.
(The interview was conducted by Dr Thomas Krämer.)