Molecular markers of radiation response in ductal carcinoma in situ
BASIC DATA OF THE RESEARCH PROJECT
ARRS code: J3-60064
TITLE: Molecular markers of radiation response in ductal carcinoma in situ
- PRICE CLASS: D
- PROJECT LEADER: Katja Goričan
- PROJECT LEADER (OI): Assist. Prof. Tanja Marinko
- LEADING ORGANISATION: University of Ljubljana (Faculty of Medicine)
- PARTICIPATING ORGANIZATION: Institute of Oncology Ljubljana
- DURATION: 1.1.2025 – 31.12.2027
- FINANCING: Slovenian Research and Innovation Agency
SHORT SUMMARY:
Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer that is most commonly detected on routine screening mammography. The incidence of DCIS has been gradually increasing over time and currently accounts for approximately 25% of newly diagnosed breast cancers and 35% of breast cancers detected in screening programs. Even though DCIS has a very good prognosis, it is also a potential precursor of invasive breast cancer that can have a significant impact on patient survival. Standard DCIS treatment mostly includes breast-conserving surgery and adjuvant radiotherapy. Radiotherapy does not significantly influence survival in DCIS, but significantly decreases local recurrence for up to 50%. However, a significant portion of patients treated with radiotherapy will experience acute or late adverse events (toxicity). There is great interindividual variability in the occurrence of radiotherapy toxicity and despite important clinical advancements in the diagnosis and treatment of DCIS, tailoring radiotherapy for individual DCIS patients remains an unmet clinical need. Additional molecular biomarkers of radiotherapy response in terms of both toxicity and disease recurrence that could be used to guide treatment selection, improving treatment outcome and patients’ quality of life are therefore needed.
On molecular level, radiotherapy can directly damage different macromolecules, especially DNA. It affects many cellular pathways and can also induce intercellular signalling through different circulating factors including non-coding RNAs, cytokines, and extracellular vesicles. Some studies have already shown that genomic, epigenetic and protein biomarkers can be associated with tumor response to radiotherapy and occurrence of toxicity. Among genomic factors, telomere length was proposed as a new genetic biomarker of radiotherapy response. Telomere length dynamics is altered after radiotherapy in DCIS patients, but the molecular mechanisms associated with this process remain largely unexplored. In recent years, studies have identified several miRNA with altered expression after radiotherapy, but their association with toxicity or their molecular effects are not yet fully understood. Additionally, plasma protein biomarkers as well as extracellular vesicles and their cargo emerged as new additional potential minimally invasive predictive biomarkers in breast cancer.
The aim of our study is therefore to (1) further define and thus expand the group of molecular biomarkers associated with response to radiotherapy in our previous studies using bioinformatic and experimental approaches and (2) to find new biomarkers of response to radiotherapy in DCIS patients. To this end, we will integrate genetic, epigenetic and protein biomarkers with clinical data and also assess the long-term response to radiotherapy in terms of late toxicity and disease recurrence. We will continue and extend a prospective longitudinal clinical study including DCIS patients treated with radiotherapy. In a clinically well-defined cohort of DCIS patients, we will then investigate molecular factors associated with miRNA expression and telomere length and evaluate new miRNA and protein biomarkers of response to radiotherapy. A validated molecular signature combining clinical data and molecular biomarkers that could help predict toxicity of radiotherapy would significantly contribute to the development of personalised treatment in DCIS.