Looking back at the 30-year history of antitumor drug development, the rapid development of molecular targeted therapy has made it a major emerging tumor treatment method after surgery, chemotherapy and radiotherapy. Since the first targeted therapy drug was approved for marketing by the U.S. Food and Drug Administration (FDA) in 1997, it has developed rapidly and become a new weapon applied in the treatment of many kinds of tumors. This article takes some of the highly prevalent cancers in China as examples to see the hope of fighting tumors brought by molecular targeted therapies. Leukemia The Philadelphia chromosome opens the door to targeted therapy As early as 1960, researchers in Philadelphia, USA, discovered a chromosomal abnormality in patients with chronic myeloid leukemia (CML). Several years later, the researchers discovered that it was the result of a translocation between the long arms of chromosomes 9 and 22. Since this chromosomal abnormality was first identified in Philadelphia, it was named the Philadelphia (Ph) chromosome. This chromosome also became the target of a targeted therapy for CML that became available 40 years later. In 2001, imatinib, the first drug proven to counteract the molecular defect of the Philadelphia chromosome, was approved for marketing in the fastest time in FDA history (after only 3 months of review) and has since become the standard treatment for CML, making CML a manageable chronic disease. The second targeted drug for CML was dasatinib, which was approved by the FDA in 2006 for imatinib-intolerant or resistant CML, and its indication was extended to initial treatment of early-stage CML in 2010. In the same year, nilotinib was approved for CML, and in 2012, bosutinib and ponatinib were approved for the treatment of CML. ■ Lung cancer From EGFR to VEGF and ALK In 1987, researchers first demonstrated that the receptor on tumor cells, the epidermal Growth factor receptor (EGFR), a receptor on tumor cells, played an important role in the growth and spread of non-small cell lung cancer. Six short years later, the first non-small cell lung cancer treatment targeting EGFR, the EGFR tyrosine kinase inhibitor (TKI) gefitinib, was approved by the FDA, and the following year a similar drug, erlotinib, was approved. In China, the self-developed erlotinib was used in the clinic in 2011. Bevacizumab, which targets vascular endothelial growth factor (VEGF), was approved by the FDA in 2006 in combination with standard chemotherapy as initial treatment for inoperable non-squamous carcinoma, which has undergone intra- or extra-pulmonary dissemination, or has recurred non-small cell lung cancer. In 2011, crizotinib, a drug targeting the mesenchymal lymphoma kinase (ALK) pathway, was approved for the treatment of ALK-positive advanced or metastatic non-small cell lung cancer. ■ Breast Cancer Benefit from Targeted Therapy for HER2-positive Patients Trastuzumab, the first targeted drug for breast cancer treatment targeting human epidermal growth factor receptor 2 (HER2), has arguably changed the fate of HER2-positive breast cancer patients. From 1998 to 2006, its indication was extended from HER2-positive advanced breast cancer to early-stage breast cancer, and in 2007, lapatinib was approved for HER2-positive breast cancer that was not effective against trastuzumab; in 2012, patuximab was also approved by the FDA with a different HER2 binding site than trastuzumab, and the combination of the two showed better efficacy. The newly approved trastuzumab-microtubule protein inhibitor DM1 chimeric drug (T-DM1) in 2013 is a new class of drug shown to significantly prolong progression-free survival and overall survival in advanced HER2-positive breast cancer. Colorectal cancer Treatment options for patients with advanced colorectal cancer In 2004, the FDA approved bevacizumab and cetuximab for the treatment of colorectal cancer. The former targets VEGF, while the latter is an EGFR inhibitor. These two drugs are also the main colorectal cancer targeted therapeutic drugs used in China’s clinical practice at present. In addition, the FDA approved the EGFR inhibitor panitumumab in 2008 and the angiogenesis inhibitor aflibercept and the multi-target tyrosine kinase inhibitor regorafenib in 2012 for the treatment of advanced colorectal cancer. Hepatocellular carcinoma Multi-molecular pathway abnormalities, breakthroughs in the midst of hardship Hepatocellular carcinoma molecular pathway research has made great progress since 2000. The findings suggest that hepatocarcinogenesis is associated with multiple pathway abnormalities, i.e., there are many different genotypes of hepatocellular carcinoma. These results explain why the development of molecularly targeted drugs for hepatocellular carcinoma is very difficult, but also provide researchers with potential explorable therapeutic targets. The breakthrough came with sorafenib, which was approved by the FDA in 2007 as the first targeted therapy for hepatocellular carcinoma after being shown in large-scale studies to extend survival in patients with inoperable advanced hepatocellular carcinoma, and soon became the standard of care.