Molecular Imaging in Cancer Chemoresistance: What’s Brewing?

Cancer therapy has advanced with molecularly targeted approaches and immunotherapy, yet chemotherapy remains essential for many aggressive cancers, including breast, lung, ovarian, pancreatic, bladder, sarcoma, and lymphomas. A major challenge is chemoresistance, in which cancer cells evade chemotherapy’s cytotoxic effects. Overexpression of adenosine triphosphate–binding cassette transporters, especially P-glycoprotein, significantly contributes to this resistance. Thus, imaging biomarkers are urgently needed to detect P-glycoprotein overexpression in vivo, identify resistant cancer cell clones, and map their distribution and heterogeneity within tumors. This article reviews the applications of SPECT, PET, and optical imaging in addressing chemoresistance. It emphasizes the potential of these modalities to enhance cancer treatment by enabling early identification of resistant clones and improving therapeutic strategies. The article outlines key steps required for the integration of molecular imaging into clinical practice, aiming to overcome chemoresistance and optimize patient outcomes.