Therapy resistance is a major problem in cancer treatments. Scientists at University Medical Center Mainz together with Alexandria University in Egypt have now identified a new mechanism for overcoming therapy resistance in head and neck tumors: The administration of the 'sunshine'-vitamin D is crucial for enhancing the effect of chemotherapy. The combination triggers the "suicide program" even in therapy-resistant tumor cells. These findings may lead not only to new combination therapies, but could also improve our understanding of nutritional supplements in cancer. The research results are published in the latest issue of the scientific journal "Cancers".

Vitamin D has a reputation for improving the survival rate in oncological diseases. However, the exact causes are still unknown. Vitamin D, which is rather a hormone than a vitamin, has a variety of functions in health and disease. Notably, vitamin D deficiency is widespread in the elderly population and especially among cancer patients. Therefore, some countries supplement the food with vitamin D.

But how does vitamin D executes its anti-cancer effects, and under what circumstances may high-dose vitamin D co-treatments help? Can vitamin D reduce therapy resistance? These challenges are explored by the research team led by Prof. Dr. Roland Stauber at the Department of Oto-Rhino-Laryngology, Head and Neck Surgery. For the treatment of head and neck tumors by chemotherapy, mainly platinum-based cytostatics are used, for example cisplatin. However, tumors can develop resistances so that the drugs have only limited effects, i.e. they do not eradicate the cancer cells efficiently. "Therapy resistance is one of the biggest challenges in cancer treatment. The underlying mechanisms are complex and, despite intensive research, have not yet been fully elucidated. This makes this research area so important', explains Prof. Stauber.

The scientists found that the combined treatment of vitamin D and cisplatin led to increased death even of cisplatin-resistant tumor cells. Vitamin D alone showed no effect on cancer cell survival. The combination caused increased formation of the so-called BIM protein in the cancer cells. This "suicide protein" initiates programmed cell death, which is a natural protective program of the cell. However, this program is often inactivated in the course of resistance development in tumor cells.

"With our results, we are laying an important foundation for further clinical investigation into combined vitamin D chemotherapy," explains Aya Khamis, first author of the study and TransMed fellow. "Also, we need to find out how relevant our discoveries are for the treatment of other tumor types of cancer, such as breast or colorectal cancer", concludes Stauber.

The study was financially supported by the German Academic Exchange Service (DAAD), the German Research Foundation (DFG), and with internal university funds.

Tumors of the pharynx, larynx, lips and oral cavity are among the ten most common types of cancer. Worldwide, they cause about five percent of tumor-related deaths. Due to the aggressive heterogeneity of these tumors, anatomic inaccessibility and high recurrence rates, survival rates for head and neck tumors have not improved significantly in recent decades. Treatment usually includes surgery, radiation, and chemotherapy or a combination of treatments.

Further information:
„The Vitamin D Receptor-BIM axis overcomes cisplatin resistance in head and neck cancer“. Khamis, A., Gül, D. et al. Cancers 2022, 14(20):5131x. DOI: 10.3390/cancers14205131

“Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance.”; Siemer, S., et al., Cancers 2021, 13, 4831.; DOI:10.3390/cancers13194831

Contacts

Univ.-Prof. Dr. Roland H. Stauber
Molekulare und Zelluläre Onkologie,
Hals-, Nasen-, Ohren-Klinik und Poliklinik – Plastische Operationen,
Universitätsmedizin der Johannes Gutenberg-Universität Mainz,
Langenbeckstr. 1, 55131 Mainz, Telefon: 06131  17-7002, Fax: 06131 17-6671;
E-Mail: rstauber@uni-mainz.de;

Aya Khamis
Molekulare und Zelluläre Onkologie,
Hals-, Nasen-, Ohren-Klinik und Poliklinik – Plastische Operationen,
Universitätsmedizin der Johannes Gutenberg-Universität Mainz,
Langenbeckstr. 1, 55131 Mainz, Telefon: 06131  17-6030, Fax: 06131 17-6671;
E-Mail: ayakhamis@uni-mainz.de

Press office:
Barbara Reinke, Corporate Communication, University Medical Center Mainz,
Phone +49 6131 17-7428, Fax +49 6131 17-3496, E-Mail:  pr@unimedizin-mainz.de