Clonal selection is a major mechanism through which tumor cells succeed in adapting to severe envi-ronmental changes and maintain their fitness.
This Darwinian process of tumor evolution is bound to generate heterogeneous profiles of driver mutations within a single lesion and across different lesions in any individual patient (intra-tumor heterogeneity).
On the other hand, tumors with the same histo-type isolated from different patients may diverge substantially in their profile of genetic drivers (inter-tumor heterogeneity) and yet share relatively homogeneous gene expression profiles and, predicta-bly, the unique biological and clinical features inherent to those shared transcriptional programs. The-se compound patterns of tumor heterogeneity pose a potential challenge to a notion of precision can-cer medicine predicated solely upon therapeutic targeting of a unique genetic driver in any individual patient.
The aim of this workshop is to critically appraise these emerging issues by a) presenting a sta-te of the art view of cancer genomic heterogeneity; b) illustrating how this knowledge can be effecti-vely leveraged for pharmacological tumor targeting in the clinic; c) showcasing examples of how com-putational systems biology and functional genomics can be exploited for identifying novel functional dependencies in cancer cells.

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