Molecular Mechanisms Contributing to Resistance to Tyrosine Kinase-Targeted Therapy for Non-Small Cell Lung Cancer

Fariz Nurwidya, Akiko Murakami, Fumiyuki Takahashi, Kazuhisa Takahashi


One of the most important pathways in non-small cell lung cancer (NSCLC) is the epidermal growth factor receptor (EGFR) pathway. This pathway aff  ects several crucial processes in tumor development and progression, including tumor cell proliferation, apoptosis regulation, angiogenesis, and metastatic invasion. Targeting EGFR is currently being intensely explored. We are witnessing the development of a number of potential molecular-inhibiting treatments for application in clinical oncology. In the last decade,  the tyrosine kinase (TK) domain of the EGFR was identifi  ed in NSCLC patients, and it has responded very well with a dramatic clinical improvement to TK inhibitors such are gefitinib and erlotinib. Unfortunately, there were primary and/or secondary resistance to these treatments, as shown by clinical trials. Subsequent molecular biology studies provided some explanations for the drug resistance phenomenon. The molecular mechanisms of resistance need to be clarified. An in-depth understanding of these targeted-therapy resistance may help us explore new strategies for overcoming or reversing the resistance to these inhibitors for the future of NSCLC treatment.



carcinoma, non-small-cell lung, mutation, drug resistance

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