The researchers from MedUni Vienna's Center for Cancer Research and cooperation partners, including MedUni Vienna's Department of Dermatology, focused their study on the protein EGFR, which is blocked by certain established cancer therapies in the fight against tumour cells. EGFR (Epidermal Growth Factor Receptor) is a receptor that is found on skin cells and controls important cell functions. Studies on hair stem cells using modern sequencing methods have shown that a disruption of the EGFR signalling pathway causes the overactivation of another signalling chain (JAK-STAT1) in the hair follicles. The resulting immune and inflammatory reactions lead to the destruction of the hair follicle stem cells and ultimately to scarring hair loss (cicatricial alopecia).
Further experiments on preclinical mouse models have shown that the progression of inflammation can be slowed down and hair growth reactivated by specifically inhibiting this signalling chain using JAK inhibitors. "Studies on skin samples from patients with scarring alopecia and from cancer patients taking EGFR inhibitors confirmed these findings," reports first author Karoline Strobl from MedUni Vienna's Center for Cancer Research. JAK inhibitors are active substances that are already used in the treatment of other autoimmune diseases such as rheumatoid arthritis.
Cancer therapies that block the EGFR receptor are established for many types of tumour, such as lung cancer or colorectal cancer, as they specifically inhibit tumour growth. However, frequent side effects of this treatment are chronic inflammation of the skin and permanent hair loss, which is very burdening for patients. In some cases, the dose of medication has to be reduced or the treatment even discontinued altogether in order to alleviate the side effects, which in turn jeopardises the success of the cancer therapy.
"Our research shows that blocking the JAK signalling chain is promising in the treatment of scarring alopecia. JAK inhibitors can specifically dampen the inflammatory process in the hair follicle and even reverse hair loss if treatment is started in good time," says study leader Thomas Bauer from MedUni Vienna's Center for Cancer Research, summarising the results. Further studies are needed to evaluate the long-term effectiveness of this therapy in patients. "This option is not only promising for cancer patients with EGFR inhibitor side effects, but also for other types of scarring alopecia for which there are currently no effective treatment options that target the mechanism of the disease," adds co-study leader Maria Sibilia, Head of MedUni Vienna's Center for Cancer Research.
Publication:
EMBO Molecular Medicine
JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia.
Karoline Strobl, Jörg Klufa, Regina Jin, Lena Artner-Gent, Dana Krauß, Philipp Novoszel, Johanna Strobl, Georg Stary, Igor Vujic, Johannes Griss, Martin Holcmann, Matthias Farlik, Bernhard Homey, Maria Sibilia and Thomas Bauer.
https://www.embopress.org/doi/full/10.1038/s44321-024-00166-3