&bgr;-Substituted γ-amino acids, &bgr;-substituted γ-amino acid derivatives, and &bgr;-substituted γ-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The &bgr;-substituted γ-amino acid derivatives and &bgr;-substituted γ-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates, capable of passing through the blood-brain barrier, and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the &bgr;-substituted γ-amino acid derivatives and &bgr;-substituted γ-amino acid analogs and (bio)isosteres and methods of using the compounds for treating tumors are also disclosed. The &bgr;-substituted γ-amino acid derivatives and &bgr;-substituted γ-amino acid analogs and (bio)isosteres exhibit an improved selectivity toward tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The &bgr;-substituted γ-amino acid derivatives and &bgr;-substituted γ-amino acid analogs and (bio)isosteres exhibit an increased efficacy on a variety of tumor types.