To Die or Not to Die, That's the Question—And the Answer May Depend on Netrin-1

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Dependence Receptors

Few fields in oncology highlight the excitement towards potential new therapies as vividly as targeted manipulations of signaling pathways, although the clinical outcome of several such therapies has been sobering. Over the past decade, there has been increasing appreciation of the concept of dependence receptors, ie, receptors that induce a specific death signal when their ligand is absent, and another (survival) signal when ligand is bound. The presence of these receptors leads to the cell becoming “dependent“ on the presence of the ligand for its survival. The group of dependence receptors includes the integrins α ₅ β ₁ and α _v β ₃ ( 1 ), the p75 neurotrophin receptor (p75NTR) ( 2 ), Patched (the human homolog of a Drosophila segment polarity gene) ( 3 ), RET (rearranged during transfection) ( 4 ) and the netrin-1 receptors DCC (deleted in colorectal cancer) and UNC5 (a family of several homologous receptors) ( 5 ). Such receptor systems, if dysregulated, may have important roles in tumor biology, although most were discovered in other systems, where they regulate development, proliferation or migration of cells.