Head and neck cancer is one of the most common cancers worldwide. Radiotherapy is an important treatment option, but it may cause long-term damage to nearby healthy tissues, especially the salivary glands. This can result in reduced saliva production and salivary gland dysfunction, negatively influencing oral health and making everyday tasks like eating and speaking difficult, significantly lowering quality of life.
Newer radiation techniques, such as proton therapy, aim to target tumors more precisely while sparing healthy tissue. However, salivary glands can still be affected. To better understand how proton and conventional (photon) radiotherapy impact salivary glands, lab-grown models known as organoids were used in this thesis of Davide Cinat. These miniature glands closely mimic the composition of real salivary glands, including rare stem cells that are essential for tissue repair and regeneration. Using these models, we discovered that proton and photon radiation induced different inflammatory responses by activating “virus-like” elements in our DNA that are normally inactive. This activation, particularly after proton radiation, led to strong inflammation and improved stem cell function. Radiation also damaged mitochondria, the energy-producing components of cells, and caused cellular aging (senescence). When we reversed this response, stem cell activity improved.
Furthermore, we found that specific signaling pathways, especially Notch and Hippo, played important roles in regulating how stem cells responded to and recovered from radiation-induced damage. By uncovering these mechanisms, this research offers valuable insights to guide the development of therapies that better protect healthy tissues, improve the effectiveness of radiotherapy, and enhance the quality of life for cancer patients.
Davide Cinat is part of MoHAD.
