Updated evidence on the mechanisms of resistance to ALK inhibitors and strategies to overcome such resistance: Clinical and preclinical data

Gouji Toyokawa, Takashi Seto

研究成果: Contribution to journalReview article査読

67 被引用数 (Scopus)

抄録

Anaplastic lymphoma kinase(ALK) rearrangement is one of the oncogenes in non-small cell lung cancer (NSCLC) identified in 2007. The PROFILE trials demonstrated that patients with ALK-rearranged NSCLC can be successfully treated with crizotinib, and that crizotinib is superior to chemotherapy in both first-and second-line settings. Furthermore, next-generation ALK inhibitors, such as alectinib and ceritinib, have been shown to harbor excellent efficacy for NSCLC patients with ALK rearrangement. However, it is known that many cases ultimately acquire resistance to ALK inhibitors. Some potential mechanisms of resistance to ALK inhibitors are as follows: ALK dominant resistance, such as secondary mutations and copy number gain in the ALK gene; activation of the bypass tracks, including EGFR, KRAS, KIT, MET, and IGF-1R. Furthermore, treatment strategies to overcome these resistance mechanisms have been proposed, and next-generation ALK inhibitors, agents which inhibit the bypass tracks, and heat shock protein 90 inhibitors are thought to be promising. Thus, clinical and pre-clinical evidence on the resistance mechanisms to ALK inhibitors and treatment strategies to overcome the resistance have been gradually obtained. Herein, we concisely review the current clinical and pre-clinical data regarding the mechanisms of resistance to ALK inhibitors and treatments to overcome such resistance.

本文言語英語
ページ(範囲)291-298
ページ数8
ジャーナルOncology Research and Treatment
38
6
DOI
出版ステータス出版済み - 6 9 2015

All Science Journal Classification (ASJC) codes

  • 血液学
  • 腫瘍学
  • 癌研究

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