The goal of personalized cancer therapy is to treat tumors based on genomic aberrations that drive their survival and progression. Most patients who receive targeted therapies typically develop resistance and disease progression within a year's time. This review focuses on the heterogeneous mechanisms of therapy resistance to tyrosine kinase inhibitors, endocrine/hormone therapy and checkpoint blockade using non-small cell lung cancer, breast and castration-resistant prostate cancer, and melanoma as classical examples, respectively. In addition, testing for resistance mechanisms and therapeutic approaches to overcoming resistance is addressed.
Keywords: Breast cancer; Castration-resistant prostate cancer; Checkpoint inhibitors; Drug resistance; EGFR T790M; ESR1 mutation; Epithelial-mesenchymal transition; Non-small cell lung cancer; Resistance mechanisms; Small cell transformation; TKI resistance.