Colorectal carcinoma (CRC) represents the 3rd most commonly diagnosed cancer in men and second in women, with more than 1.2 million new cancer cases and 600 000 deaths only in 2008. A recent hypothesis is based on a direct relationship between angiogenesis and colorectal cancer stem cells (CR-CSCs) proliferation, this interaction being the cornerstone of initial response encountered during biological treatment. The concept of the REACT proposal will comprise the assessment of tumor microenvironment of advanced CRC patients, with the aim of improving overall survival.
Key objectives of the REACT proposal include: (1) Real-time imaging evaluation of colorectal cancer stem cells (CR-CSCs) and fine tuning of biological therapy based on imaging follow-up with either eCLE or pCLE; (2) Better stratification of prognosis and treatment response (including PFS and OS), based on imaging methods, validated by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR).
The project starts from clinical and imaging (confocal laser endomicroscopy) characteristics of advanced CRC patients (assessment of CSCs), validated through a detailed basic research methodology involving pathology and molecular biology techniques (immunohistochemistry and real-time PCR). The use of minimal invasive imaging techniques will pave the way for real-time assessment of key markers of CR CSCs, allowing stratification of patient subgroups and individual tailoring of the biological therapy. The same procedures would possibly allow a sensitive monitoring of CRC stem cells, in unresectable metastatic cases, before and during chemoradiotherapy and/or antiangiogenic therapy.