Tyrosine kinases are implicated in tumorigenesis and progression, and have emerged as major targets for drug discovery. Tyrosine kinase inhibitors (TKIs) inhibit corresponding kinases from phosphorylating tyrosine residues of their substrates and then block the activation of downstream signaling pathways. Over the past 20 years, multiple robust and well-tolerated TKIs with single or multiple targets including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT have been developed, contributing to the realization of precision cancer medicine based on individual patient’s genetic alteration features. TKIs have dramatically improved patients’ survival and quality of life, and shifted treatment paradigm of various solid tumors. In this article, we summarized the developing history of TKIs for treatment of solid tumors, aiming to provide up-to-date evidence for clinical decision-making and insight for future studies.

Despite the demonstrated benefit from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) based therapies, EGFR mutant lung adenocarcinoma will eventually acquire drug resistance. Transformation to small-cell lung cancer (SCLC) is considered to be a rare resistance mechanism of EGFR-TKI therapy.We describe a case of a 46-year-old man presenting with refractory cough. Percutaneous transthoracic biopsy was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient relapsed after successful treatment with gefitinib for 1 year, at which point rebiopsy identified an SCLC and chemotherapy composed of platinum and pemetrexed was started. However, despite the brief success of chemotherapy, our patient died of aggressive cancer progression and complications of chemotherapy.Our case highlights the importance of rebiopsy when managing drug resistance and presents a possible origin of the transformed cells. We also summarize the clinical characteristics of cases involving transformed SCLC from previous studies and discuss whether it could be a new subtype of SCLC.