Oncogene addiction: pathways of therapeutic response, resistance, and road maps toward a cure

A key goal of cancer therapeutics is to selectively target the genetic lesions that initiate and maintain cancer cell proliferation and survival. While most cancers harbor multiple oncogenic mutations, a wealth of preclinical and clinical data supports that many cancers are sensitive to inhibition of single oncogenes, a concept referred to as ‘oncogene addiction’. Herein, we describe the clinical evidence supporting oncogene addiction and discuss common mechanistic themes emerging from the response and acquired resistance to oncogene‐targeted therapies. Finally, we suggest several opportunities toward exploiting oncogene addiction to achieve curative cancer therapies. Graphical Abstract The term ‘oncogene addiction’ refers to the fact that cancer cells depend on relatively few oncogenes to sustain a malignant phenotype. This review summarizes our current understanding of this process and how it can be exploited in cancer therapy.