Projects / Programmes
Identification of molecular biomarkers for prognosis of clinical outcome and metastasis in triple negative breast cancer patients.
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B570 |
Biomedical sciences |
Obstetrics, gynaecology, andrology, reproduction, sexuality |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
biomarkers, triple negative breast cancer, prognostic models, metastaze
Researchers (19)
Organisations (2)
Abstract
Triple negative breast cancer (TNBC) represents a subtype of breast cancer with a poor prognosis. It represents approximately 10 – 20 % of all breast cancers. Recent research has still been unable to answer what are the best ways of early TNBC detection, predicting clinical progression (aggressiveness, metastasis) and treatment optimization. Due to the least well defined target treatment of all BC subtypes, patients have a poor prognosis and high risk for development of local recurrence and metastasis. TNBC treatment is therefore done aggressively. However, not all treatment needs to be done as aggressively as once thought. Therefore needs for stratification and the personalization have arisen. This project aims to identify through the integration of genetic (genotypization and detection of circulating tumor DNA in plasma), expression (RNAseq), epigenetic (DNA modifications) and regulatory (profiling of noncoding RNA, alternative splicing) data with bioinformatics tools (Gene Ontology) biological pathways important in the biology and characteristics of TNBC. We expect to analyse more than 150 tissue samples of patients with TNBC. Blood as well as tissue samples of additionally approximately 50 patients with TNBC will be prospectively included in this study. The discoveries through this projects will lead to: i) improved knowledge on non-invasive biomarkers on identifying the aggressiveness of disease and intention to metastasize, ii) the development of a diagnostic algorithm linking the already known clinical parameters, pathological parameters and genetic/molecular data together, thus enabling the optimal treatment method for patients and further monitoring of patients with diagnosed TNBC and ii) the development of targets for therapeutics in TNBC.
Significance for science
This project will examine genetic mechanisms related to risk and development of TNBC, which will bring important contributions in Slovenia at both medical and societal levels:
1. The project will enable personalized treatment of women with TNBC based on their genetic profiles (Res. Pract., 2017 213: 177-82). Individualized treatment based on molecular biomarkers will represent optimal therapy that will lead to fewer side effects.
2. Individualized treatment, which is more cost-effective, will bring savings to the public health budget.
3. The data gathered in the project about specific genetic mutations and their associations with clinical outcomes will contribute to our knowledge about the mechanisms of malignant breast tumor development. It will enable better disease prevention and treatment. The research based on genetic analyses provides an opportunity for improved screening for TNBC. According to the findings of our research, it will be possible to create individualized risk profiles, which will reduce the use of unnecessary aggressive treatments, and enhance diagnostic procedures for high-risk patients.
4. Given the difficulty of clinical treatment and management of TNBC patients, our project aims to enhance our understanding of how to manage patients after TNBC diagnosis. A recent meta-analysis has highlighted that certain TNBC subtypes (e.g. patients with the BL1 subtype) respond better to therapy with specific chemotherapeutics (DNA destabilizers and angiogenesis inhibitors) than others. Our findings on patient genetic characteristics will help better predict which therapy is appropriate for patients with individual subtypes of TNBC and create personalized therapy based on genetic data.
5. By integrating genotypic / transcription / epigenetic / circulating tumor DNA data, it will be possible to create commercial diagnostic biomarker analyses (either in the form of diagnostic packages or patent applications).
Significance for the country
This project will examine genetic mechanisms related to risk and development of TNBC, which will bring important contributions in Slovenia at both medical and societal levels:
1. The project will enable personalized treatment of women with TNBC based on their genetic profiles (Res. Pract., 2017 213: 177-82). Individualized treatment based on molecular biomarkers will represent optimal therapy that will lead to fewer side effects.
2. Individualized treatment, which is more cost-effective, will bring savings to the public health budget.
3. The data gathered in the project about specific genetic mutations and their associations with clinical outcomes will contribute to our knowledge about the mechanisms of malignant breast tumor development. It will enable better disease prevention and treatment. The research based on genetic analyses provides an opportunity for improved screening for TNBC. According to the findings of our research, it will be possible to create individualized risk profiles, which will reduce the use of unnecessary aggressive treatments, and enhance diagnostic procedures for high-risk patients.
4. Given the difficulty of clinical treatment and management of TNBC patients, our project aims to enhance our understanding of how to manage patients after TNBC diagnosis. A recent meta-analysis has highlighted that certain TNBC subtypes (e.g. patients with the BL1 subtype) respond better to therapy with specific chemotherapeutics (DNA destabilizers and angiogenesis inhibitors) than others. Our findings on patient genetic characteristics will help better predict which therapy is appropriate for patients with individual subtypes of TNBC and create personalized therapy based on genetic data.
5. By integrating genotypic / transcription / epigenetic / circulating tumor DNA data, it will be possible to create commercial diagnostic biomarker analyses (either in the form of diagnostic packages or patent applications).
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
