Recent advances in molecular targeted therapies have greatly improved treatment 
outcomes for cancers driven by oncogenic mutations. Despite initial and dramatic 
clinical responses, tumors eventually acquire resistance to these targeted 
therapies, showing flexible and diverse responses. Interestingly, cancer cells 
sometimes overadapt to the drug treatment environment, leading to a state in 
which cancer cells cannot survive without the drug. This interesting phenomenon 
(often called "drug dependency" or "drug addiction") is exemplified in 
preclinical acquired resistance models of BRAF-mutated melanoma treated with 
vemurafenib and EGFR-mutated lung cancer treated with EGFR tyrosine kinase 
inhibitors. A number of intriguing parallels in drug-addicted cancers became 
apparent in a comparison of the two models: (i) overexpression of driver 
oncogenes as causes of acquired resistance; (ii) overexpression of driver 
oncogenes causing MEK-ERK hyperactivation under drug-free conditions; (iii) 
hyperactivation of the MEK-ERK pathway as critical to this drug addiction 
phenomenon; (iv) ongoing dependence on the oncogenic driver; and (v) morphologic 
changes in resistant cells under drug-free conditions. This Perspective article 
not only focuses on this interesting and peculiar phenomenon but also discusses 
weapon strategies to exploit this unintentional weakness of cancers.