Molekularni napovedni dejavniki odgovora na zdravljenje z obsevanjem pri raku dojk
Molecular predictors of radiation treatment response in breast cancer
OPIS PROJEKTA
Duktalni karcinom in situ (ductal carcinoma in situ, DCIS) je neinvazivna proliferacija neoplastičnih celic v duktusu mamarne žleze, ki predstavlja okrog 20 % novo ugotovljenih rakov dojk. Lahko se razvije tudi v invazivno obliko raka dojk. DCIS zdravimo kirurško in z obsevanjem. Z obsevanjem pomembno izboljšamo lokalno kontrolo bolezni.
Po drugi strani pa z obsevanjem pri večini bolnic povzročamo akutne in kasne neželene učinke, ki pomembno vplivajo na kvaliteto življenja. Med bolnicami z rakom dojk obstajajo velike razlike v pojavnosti neželenih učinkov po obsevanju. Glavni izziv je torej, kako v naprej napovedati in s tem omejiti toksičnost, ne da bi zmanjšali učinkovitost zdravljenja. Trenutno v klinični praksi nimamo metode, s pomočjo katere bi napovedali možnost pojava neželenih učinkov sevanja pri posamezniku in mu na podlagi tega prilagodili zdravljenje.
Potrebni bi bili torej zanesljivi in enostavni molekularni napovedni dejavniki odgovora na zdravljenje z obsevanjem, ki bi lahko omogočili stratifikacijo bolnic in izbor zdravljenja DCIS, zmanjšali pojav neželenih učinkov in izboljšali izid zdravljenja.
Namen naše raziskave je torej identifikacija novih molekularnih napovednih dejavnikov odgovora na zdravljenje z obsevanjem pri bolnicah z DCIS z integracijo bioinformatskih podatkov, genetskih in plazemskih označevalcev.
Najprej bomo nove potencialne biološke označevalce odgovora na zdravljenje z obsevanjem poiskali s pomočjo preučevanja bioloških poti in bioinformatskih pristopov. Nato bomo te potencialne genetske in plazemske označevalce preverili na klinično dobro definirani skupini bolnic z DCIS, zdravljenih z dopolnilnim obsevanjem.
Pripravili bomo tudi multivariatne napovedne modele odgovora na zdravljenje z obsevanjem, ki bodo združevali klinične dejavnike, parametre obsevanja ter molekularne dejavnike in bodo omogočili prenos naših rezultatov v klinično prakso in personalizacijo zdravljenja z obsevanjem.
BRIEF DESCRIPTION OF THE PROJECT
Ductal carcinoma in situ (DCIS) is a non-invasive proliferation of neoplastic cells within the duct of the mammary gland that represents around 20% of newly diagnosed breast cancers. It is a potential precursor of invasive breast cancer. DCIS patients are treated with surgery and radiation treatment. Radiation treatment enables significantly better local control.
However, most of patients treated with radiation will experience acute or late adverse events that importantly decrease patient’s quality of life. There is great interindividual variability in occurrence of adverse events and the key challenge is therefore how predict and to limit the toxicity without compromising the efficacy of the treatment. At the moment, there is no management strategy that would allow treatment personalisation regarding the risk of adverse events in clinical practice.
Reliable and easy to use molecular predictors of radiation treatment response that would enable patient stratification and treatment selection in DCIS, limiting adverse events and improving treatment outcome are therefore needed.
The aim of our study is therefore to find novel molecular predictors of radiation treatment response in DCIS patients by integrating bioinformatics data, genetic and plasma biomarkers.
We will first identify novel potential biomarkers of radiation treatment response using pathway based and bioinformatic approaches.We will then investigate these potential genomic and plasma biomarkers in a clinically well-defined cohort of DCIS patients receiving adjuvant radiation treatment.
We will also prepare multivariable predictive models of radiation treatment response integrating the clinical, radiation therapy parameters and biomarker data that will enable translation of our results in the clinical practice for personalization of radiation treatment.
FINANCIRANJE / FINANCING
ARRS
Veda 3.04 Medicinske vede / Onkologija
Research activity 3.04 Medical sciences / Oncology
