Published 13 January 2022 by Perparim Limani

New Drug for Cancer Treatment on Track

Allosteric effector on the hemoglobin molecule: ITPP reduces oxygen binding to hemoglobin. Photo/Credit: Courtesy of Perparim Limani

A master class at the 64th Lindau Nobel Laureate Meeting 2014 (Physiology/Medicine) was an important milestone for Lindau Alumnus Perparim Limani for the development of a new approach to the treatment of cancer.

We developed our new therapy concept for the fight against tumours together with Prof. Pierre-Alain Clavien, Director, and my co-fellow Dr Marcel Schneider from the Swiss Centre for Liver and Pancreatic Diseases at the University Hospital Zurich in cooperation with colleagues from oncology. This project was the basis of my doctoral thesis. The close collaboration with the research group of Nobel Laureate Jean-Marie Lehn with regard to the use of the molecule Inositol Trispyrophosphate (ITPP) was very important. After he and his group had developed this molecule, Professor Lehn was looking for physicians to test applications.

Oxygen supply as a central point

A central starting point of our idea is the oxygen supply of the tumour. In the early stages, the tumour is supplied with oxygen via the diffusion. If the tumour grows after a while, hypoxia occurs. As a result, the tumour changes its phaenotype and its mechanism – metastases are forming. The innovation of our approach is the use of ITPP as an allosteric effector on hemoglobin, which allows more oxygen to reach the tumours and their environment.

Chemical structure of ITPP
Chemical structure of ITPP. Photo/Credit: Courtesy of Perparim Limani

Previous therapies focus more on reducing oxygen intake. In our preclinical studies, we were able to show that the use of the ITPP developed by Jean-Marie Lehn significantly inhibits tumour growth. We anticipated a similar situation in patients. In our clinical trial prior to the initiation of standard therapy such as chemotherapy, surgery or radiation participants received five to nine infusions of ITPP and were medically supervised.

Input from Lindau

Although I had already been in contact with Prof. Jean-Marie Lehn and his colleagues through my project, my participation in his master class during the 64th Lindau Meeting provided an important impetus for our work. The exchange with physicians and biologists from different research fields from all over the world was very helpful, for example to discuss animal models, optimise the setting of study drug administration and discuss the selection of patients for clinical trials.

Perparim Limani during #LINO14
Master Class with Jean-Marie Lehn

Prof. Jules A. Hoffmann provided me with valuable information on methods for working in the laboratory, and Prof. Ferid Murad discussed aspects of biochemistry. I was also able to expand my scientific network. I am connected to many Lindau Alumni via social media and follow their work. For example, I was able to contact another participant to test a diagnostic device, and so easily found out that it was not the right one for my work.

This is also my advice for future young scientists coming to Lindau: Enjoy the diverse programme and the insights into the work of Nobel Laureates and researchers from all over the world. The same motto actually applies to the daily work. I wouldn’t pursue a career plan. I’d take pleasure from my work. You don’t know in advance what results you’re going to get anyway, because you have to break new ground again and again – that’s the principle of science. With this attitude, we will also begin Phase II clinical trials of our new therapeutic approach in spring 2022. The development of new drugs is usually a long way to go.

Perparim Limani

Perparim Limani is a senior physician and scientist at the Department of Surgery and Tranplantation at the University Hospital Zurich. He studied medicine at the University of Zurich, where he also completed his doctoral thesis. Afterwards, he gained experience at various clinics and institutes in Switzerland and the USA. In 2014, he was one of the selected young scientists who took part in the 64th Lindau Nobel Laureate Meeting to present his scientific projects in a master class.