Background
Cancer progression involves concomitant acquisition by neoplastic cells of two key biological properties: (i) the ability to migrate, invade and colonize distant organs, and (ii) resistance to anticancer treatments. We conceived a systematic approach based on genome-wide screenings in cellular models and leading to identification of genes or groups of genes (“signatures”) conferring such properties. Functional analysis and extensive molecular profiling of cancer samples subsequently allows exploiting the genes as therapeutic targets, and the signatures as diagnostic tools for personalized therapy.
Achievements
The Laboratory has developed technologies to screen the whole genome for genes promoting cancer aggressiveness and resistance to treatment. As an example, with the “xenoarray” functional screening technology we identified the GAB2 gene as a key promoter of anchorage independence, a property that renders cancer cells capable of surviving and proliferating also when detached from the tumour mass. By gene expression profiling, we then defined “GAB2-signature” composed of about 200 genes regulated during GAB2-driven anchorage independence. Interestingly, expression of the GAB2-signature is associated to breast cancer metastatic relapse and response to neoadjuvant treatment. Gene expression profiling has also been conducted on over 130 liver metastases of colorectal cancer, which allowed preliminary definition of transcriptional signatures associated to KRAS mutation status, RAS pathway activation and response to therapeutical EGFR inhibition.
Goals
The Laboratory aims at the following integrated goals: (i) Systematic search for genes modulating cancer cell invasive/metastatic ability or responsiveness to targeted therapy; (ii) exploitation of these genes as additional therapeutical targets, or as diagnostic indicators of metastatic aggressiveness or resistance to treatment; (iii) definition of genomic signatures in cell-based models of cancer progression and treatment resistance, and subsequent validation of their clinical value; (iv) genomic profiling of colorectal cancer to find molecular signatures associated to metastatic progression, mutational status and response to targeted treatments.
Internal collaborations
Transcriptional responses to oncogenic mutations (Molecular Genetics); Transcriptomics of endothelial cells (Vascular oncology); Cancer stem cell transcriptomics, transcriptional responses of cancer cells to target therapy and to radiation therapy (Cancer Stem Cell Lab); Genomic profiling of colorectal cancer (Surgical Oncology, Medical Oncology, Pathology, Radiology, Nuclear Medicine, Molecular Pharmacology); Genomic profiling of rectal cancer (Gastroenterology, Radiation Therapy, Surgical Oncology, Medical Oncology, Pathology, Radiology, Nuclear Medicine)
