Amino acid proline key to promising new treatment strategy for myeloma patients

Multiple myeloma, also known as Kahler’s disease, is a blood cancer in which uncontrolled growth of plasma cells occurs in the bone marrow. This large amount of abnormal cancer cells takes the place of other cell types, such as red blood cells, platelets or normal white blood cells, which also impairs their functions. As a result, patients often experience anaemia, bruising and prolonged bleeding, as well as an increased risk of infection. Every year, about 1,000 patients in Belgium are told that they suffer from multiple myeloma. About 40% of these will die within five years.

Incurable disease

The Hematology and Immunology research group, part of VUB’s Oncology Research Center, has been carrying out successful research into this blood cancer for years. Since this disease is still incurable, these researchers continue to do their utmost to investigate its development and progression and to test new treatment methods.

Discovery of the role of proline

Over the past three years, the research team has focused on what nutrients these cancer cells need to keep growing. One of these nutrients turned out to be proline, an amino acid needed for protein production, but also for DNA/RNA production, the removal of toxins from the body and the production of energy. An initial experiment showed that myeloma cells converted more glutamine to proline when cultured in a low oxygen environment, a typical feature of the natural bone marrow environment. Proline production itself was also increased in an oxygen-deficient environment. Furthermore, myeloma patients in relapse also showed higher expression of the PYCR gene, which is responsible for proline production.

Initial tests

To see if proline inhibition would be a good treatment option, cancer cells were treated in the lab with a PYCR inhibitor, as well as PYCR gene expression blocked using small interfering RNA. PYCR inhibition reduced the viability and multiplication of the cancer cells, and also caused cell death of the cancer cells. Further investigation into the underlying changes showed that the PYCR gene is important for protein, DNA and RNA production and that PYCR inhibition reduced these processes, leading to slowed cell growth of the cancer cells and ultimately their cell death.

Promising results

Myeloma patients are currently treated with a combination therapy consisting of multiple drugs including Velcade. To evaluate whether PYCR inhibition could also be part of this, myeloma cells were treated simultaneously with Velcade and the PYCR inhibition. It was found that the combination therapy induced more cell death of cancer cells compared to the individual therapies. This combination therapy was also tested on diseased myeloma-carrying mice, where again it was able to better inhibit the disease.

Award-winning research

This research was awarded the American Society of Hematology Abstract Achievement Award at the annual hematology congress in Atlanta, USA in December 2021. It was also accepted for publication on January 7 2022 in the Journal of Experimental and Clinical Cancer Research.

VUB and cancer research

VUB is an Urban Engaged University that is firmly committed to the fight against cancer through scientific research. Scientists from various fields – medicine, bioengineering, pharmacy, physiotherapy, psychology – work together on an interdisciplinary basis. Fundamental and clinical scientific research into cancer go hand in hand, which is why the UZ Brussel, VUB’s university hospital, is an important partner in research, therapy and care. More awareness about cancer is needed for its prevention and cure, while more awareness about scientific research benefits the search for remedies and patient well-being. VUB is therefore grateful for an initiative such as World Cancer Day on 4 February.

The VUB Foundation helps to secure financial resources for research. With the VUB Yamina Krossa Fund, the VUB Foundation supports breast cancer research and the development of a potential cancer vaccine by Professor Damya Laoui and her team (VUB-VIB). The VUB-UZB Paul De Knop Fund is another initiative, established by the former VUB rector who was diagnosed with melanoma shortly after his mandate ended. During treatment by Prof Bart Neyns and his team at the UZ Brussel, Paul De Knop underwent immunotherapy, a promising immune system-based cell therapy. As a grateful patient, he set up the fund to help more people in need of treatment, quickly and more affordably.

Want to know more? Contact Isabelle Marneffe ([email protected]), director of the VUB Foundation. www.vubfoundation.be