Hitting the Mark in Hamartoma Syndromes

The missed mark or hamartia underlying each hamartoma syndrome is a mutation in a tumor suppressor gene. This sets the stage for the development of frequent and early tumors in multiple organs. Loss of function of the tumor suppressor in neoplastic cells leads to dysregulation of signaling pathways and tumor growth. The convergence of these signaling pathways to the mTOR pathway suggests that rapamycin or rapamycin-like drugs have potential for treatment, perhaps in combination with drugs targeting other signaling pathways. Haploinsufficient cells also play significant roles in tumor formation. Disrupting interactions between neoplastic cells and surrounding haploinsufficient cells using antiangiogenesis therapies represent an additional approach for treatment. It is hoped that the debilitating effects of these syndromes soon will be alleviated or even reversed though targeted therapies.