INFORMAZIONI SU
GAVA Chiara
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Supervisore: Dr.ssa Spessotto
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| Breast cancer (BC) is the second leading cause of cancer death among women worldwide and Luminal Breast Cancer (LBC, ER+, PR+/-, HER2 not amplified) represents the most common BC subtype, accounting for ~70% of all BC. Since alterations of the PI3K/AKT/mTOR pathway represent key events in LBC oncogenesis and drug resistance, we will perform a loss-of-function (LOF) CRISPR-Cas9 screening, targeting the entire druggable genome, to identify new targets that may alter the viability of PIK3CA mutated LBC cells. To this aim, we will employ luminal breast primary epithelial cells (BPE) for which we have generated stable cell clones carrying PIK3CA mutation and aim at identifying putative genes whose down-modulation (by CRISPR-Cas9 KO) is synthetic lethal with standard therapy (Tamoxifen). Emerging candidates will then be further evaluated in a second and more targeted “validation screening”, aimed at reducing the number of genes that will be eventually tested in vitro and in vivo. By this approach, we expect to take a promising step toward a better tailoring of the treatments for LBC patients. | |