Non-invasive PET Imaging of CDK4/6 Expression in Breast Cancer Models

1036Introduction: Breast cancer is a worldwide health issue with about 1 million new cases every year. Dysregulated cellular proliferation, a common feature to all human cancers, is a key player of aberrant proliferative signaling and is therefore considered as a "hallmark of cancer". In breast cancer, a lot of attention focuses on particular members of the cell cycle machinery, the D-type cyclins and their partner cyclin-D kinases 4 and 6 (CDK4/6). CDKs are serine/threonine kinases key in regulating cell cycle progression by associating with cyclins. Several studies have identified alterations of cell cycle regulators in human breast cancer and provide a strong rationale for a therapeutic role for CDK4/6 inhibition in this tumor type. Amplification of the cyclin-D1 occurs in about 20% of human breast cancers, while overexpression of the protein is above 60%. The subtype for which CDK4/6 inhibition has the strongest rationale is estrogen receptor (ER)-positive disease. These subtypes almost always retain Rb function, thereby CDK4 and CDK6 targeting agents can block pRb phosphorylation (in low nanomolar concentration) and induce G1 arrest in sensitive cell lines. It is often controversial whether CDK4/6 inhibitors are capable to prolong overall survival. Moreover, it is urgent to find a way to select which patients are most likely to benefit from these drugs and to monitor, non-invasively, the progress of the disease and the overall treatment response. To this aim, we develope...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Preclinical Probes for Oncology Posters Source Type: research