Cancer is notorious for relapsing after treatment. Such relapses are driven by tumor-initiating cells, a type of stem cell that gives rise to tumors. Damelin et al. determined that a protein called PTK7 is frequently present on tumor-initiating cells and developed an antibody-drug conjugate targeting it. In mouse models of several tumor types, the therapy reduced tumor-initiating cells and outperformed standard chemotherapy. The antibody-drug conjugate also reduced tumor angiogenesis and promoted antitumor immunity, possibly contributing to its effectiveness.