Tumor-Microenvironment related changes as new tools for early detection and assessment of high-risk disease

Progetto: Research project

Dettagli progetto

Description

An emerging area of interest in cancer research is the investigation of tumor microenvironment, itscellular and molecular components, the reciprocal interactions between tumor cells and thesupporting stromal cells, and the dynamic framework of the extracellular matrix that they build andremodel. A growing number of studies demonstrated significant correlations betweenmicroenvironment components and patients’ outcome, thereby emphasizing their relevance totumor progression. Extensive changes occur in the stromal compartment during cancer evolution. Infact, tumor cells actively recruit bone marrow-derived cells into their microenvironment to facilitateprimary tumor development and progression, and a continuous inter-cellular cross-talk is ensuredby the release of soluble molecules and vesicles containing proteins, mRNA and microRNA, alsodetectable in the blood and currently recognized as the main mechanism underlying cell-to-cellcommunication acting either locally or systemically.Despite the increasing awareness that stroma interactions contribute to tumor development andprogression, not enough attention has been devoted either to stroma modifications occurring inpremalignant lesions, or to how normal tissue, surrounding the primary tumor and away from it,differently signals the molecules with a key role in cancer initiation and progression.A better understanding of early stroma modifications induced by tumor cells, and viceversa (cancercells modifications induced by stroma), could have a profound impact on how cancer is detected,prevented and treated, and might provide blood and tissue-based biomarkers able to identifyprogressing lesions. Such a novel perspective might improve early cancer detection and allowidentification of aggressive tumors, thereby overcoming the well-known limitations of currentscreenings and diagnostic approaches that, apart from causing anxiety, exposing to potentiallyharmful amounts of radiation and being expensive to the health care system, are also unable topredict the biological aggressiveness of the detected lesion.Our project intends to answer the questions of this call on the basis of the hypothesis that in theearly stages of neoplastic transformation, the microenvironment surrounding the mutated cells couldhave a pivotal role in tumor initiation and progression. In particular, microenvironmentalcharacteristics could affect the subsequent development of the lesion, determining ab initio itsbehavior as an aggressive or indolent cancer. This idea will be challenged both on experimentalmodels and on clinical specimens of lung, colorectal, prostate and breast cancer, and melanoma.We intend to perform an extensive molecular profiling of tumor cells of their microenvironment andplasma/serum samples, in order to determine and characterize the interactions among thesecomponents in both surrounding and distant tissues, and we will use a whole genome scanningtechnique in order to identify possible elements of individual genetic predisposition as indicators ofvarious levels of potential cancer aggressiveness. The present proposal is based on a validatedmultidisciplinary approach and takes advantage of screening trials ongoing for lung and colorectalcancers, of an ongoing international project of active surveillance for prostate cancer and of solidretrospective studies for breast cancer and melanoma; within this framework, we intend toinvestigate the following topics:1. relevance of cells and molecules from and to bone marrow for early diagnosis and riskassessment2. diagnostic value of signals from tumor microenviron

Layman's description

Our project intends to answer the questions of this call on the basis of the hypothesis that in theearly stages of neoplastic transformation, the microenvironment surrounding the mutated cells couldhave a pivotal role in tumor initiation and progression. In particular, microenvironmentalcharacteristics could affect the subsequent development of the lesion, determining ab initio itsbehavior as an aggressive or indolent cancer. This idea will be challenged both on experimentalmodels and on clinical specimens of lung, colorectal, prostate and breast cancer, and melanoma.We intend to perform an extensive molecular profiling of tumor cells of their microenvironment andplasma/serum samples, in order to determine and characterize the interactions among thesecomponents in both surrounding and distant tissues, and we will use a whole genome scanningtechnique in order to identify possible elements of individual genetic predisposition as indicators ofvarious levels of potential cancer aggressiveness. The present proposal is based on a validatedmultidisciplinary approach and takes advantage of screening trials ongoing for lung and colorectalcancers, of an ongoing international project of active surveillance for prostate cancer and of solidretrospective studies for breast cancer and melanoma; within this framework, we intend toinvestigate the following topics:1. relevance of cells and molecules from and to bone marrow for early diagnosis and riskassessment2. diagnostic value of signals from tumor microenvironment and extracellular matrix3. tumor-microenvironment interactions and genetic risk4. clinical impact of tumor-microenvironment related changes
StatoFinito
Data di inizio/fine effettiva1/1/1512/31/16