The remarkable antitumor activity of the designed recombinant protein-drug conjugate with star-shaped structure in both small and large tumor models can be attributed not only to the triple targeting against EGFR, HER2, and integrin α<sub>v</sub>β<sub>3</sub>, but also to the "site effect" of targeting elements in heterotrimeric fusion proteins brought by the unique topological structure. Here, ERBB2 is linked to neoplasm.