Increased glycolysis has been one of the metabolic characteristics known as the Warburg effect.
The functional and therapeutic importance of the Warburg effect in targeted therapy is scientifically
recognized and the glucose metabolic pathway has become a desirable target of anticancer strategies.
Glucose transporters (GLUTs) play an important role in cancer glycolysis to sustain cancer cell proliferation,
metastasis and survival. Utilizing the knowledge of differential expression and biological functions
of GLUTs offers us the possibility of designing and delivering chemotherapeutics toward targeted
tumor tissues for improved cancer selectivity. Inhibition of glucose uptake or glycolysis may effectively
kill hypoxic cancer cells. Facilitative drug uptake via active transportation provides the potential opportunity
to circumvent the drug resistance in chemotherapy. GLUTs as the hallmarks and biotargets of
cancer metabolism enable the design and development of novel targeted theranostic agents. In this updated
review, we examine the current scenario of the GLUTs as strategic targets in cancer and the
unique concepts for discovery and development of GLUTs-targeted anticancer agents. We highlight the
recent progresses on structural biology and underlying mechanism studies of GLUTs, with a brief introduction
to the computational approaches in GLUT-mediated drug transport and tumor targeting.