The present invention provides a powerful tool to identify personalized therapeutic strategies. In particular, the invention provides methods for determining therapeutically targetable dominant signaling pathways in a cancer sample from a subject affected with a solid cancer, determining a treatment protocol for the subject, selecting a subject for a therapy, determining whether the subject is susceptible to benefit from a therapy, predicting clinical outcome of the subject, treating the subject and/or predicting the sensitivity of a solid cancer to a therapy.