DNA-damaging agents, such as platinum, gemcitabine, and 5-fluorouracil (5-FU), are the primary chemotherapy drugs used to treat many cancers. These drugs cause cell cycle arrest by impeding DNA synthesis, replication, and transcription, to eventually induce cancer cell apoptosis or mitotic catastrophe78. For lung cancer, platinum agents are indispensable in the standard chemotherapy doublet regimens. Evidence-based clinical practice shows that two-drug combinations are an optimal chemotherapy regimen for the treatment of advanced NSCLC. The combinations of cisplatin or carboplatin with either one of the DNA-damaging agents (gemcitabine), tubulin-targeting drugs (paclitaxel, docetaxel, or vinorelbine), or DNA topoisomerase II inhibitors (VP-16), show almost similar response rates and survival time for unselected NSCLC9. Therefore, clinically applicable biomarkers for prediction of the efficacy of combination chemotherapy are urgently needed for personalized chemotherapy treatment of NSCLC.