MET kinase inhibitor reverses resistance to entrectinib induced by hepatocyte growth factor in tumors with NTRK1 or ROS1 rearrangements

Entrectinib is an effective drug for treating solid tumors with NTRK gene rearrangement and non‐small cell lung cancer (NSCLC) with ROS1 gene rearrangement. However, its efficacy is limited by tolerance and acquired resistance, the mechanisms of which are not fully understood. The growth factors produced by the tumor microenvironment, including hepatocyte growth factor (HGF) produced by tumor‐associated fibroblasts, critically affect the sensitivity to targeted drugs.

[1]  M. Mino‐Kenudson,et al.  Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms. , 2021, Cancer cell.

[2]  Yi-long Wu,et al.  A phase Ib study of the highly selective MET-TKI savolitinib plus gefitinib in patients with EGFR-mutated, MET-amplified advanced non-small-cell lung cancer , 2020, Investigational New Drugs.

[3]  Minoru Terashima,et al.  Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer , 2020, Nature Communications.

[4]  H. Groen,et al.  Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer. , 2020, The New England journal of medicine.

[5]  Ying Cheng,et al.  Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. , 2020, The Lancet. Respiratory medicine.

[6]  A. Drilon,et al.  Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. , 2019, The Lancet. Oncology.

[7]  A. Drilon,et al.  Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. , 2019, The Lancet. Oncology.

[8]  A. Drilon,et al.  TRK inhibitors in TRK fusion-positive cancers , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  Amanda R. Kulick,et al.  Resistance to TRK inhibition mediated by convergent MAP kinase pathway activation , 2019, Nature Medicine.

[10]  Yasuyoshi Watanabe,et al.  Macrocyclic peptide-based inhibition and imaging of hepatocyte growth factor , 2019, Nature Chemical Biology.

[11]  S. Yano,et al.  AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells , 2019, Nature Communications.

[12]  D. Hong,et al.  Emerging Targeted Therapy for Tumors with NTRK Fusion Proteins , 2018, Clinical Cancer Research.

[13]  Ryohei Katayama,et al.  Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1-Rearranged Cancers , 2017, Molecular Cancer Therapeutics.

[14]  R. Roskoski.  ROS1 protein-tyrosine kinase inhibitors in the treatment of ROS1 fusion protein-driven non-small cell lung cancers. , 2017, Pharmacological research.

[15]  M. Yashiro,et al.  Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia , 2016, PloS one.

[16]  P. Chiao,et al.  Amphiregulin in Cancer: New Insights for Translational Medicine. , 2016, Trends in cancer.

[17]  E. Giovannetti,et al.  Entrectinib: a potent new TRK, ROS1, and ALK inhibitor , 2015, Expert opinion on investigational drugs.

[18]  M. Kawaguchi,et al.  Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues , 2014, Cancers.

[19]  A. Bardelli,et al.  Acquired resistance to EGFR‐targeted therapies in colorectal cancer , 2014, Molecular oncology.

[20]  T. Tokuyasu,et al.  Gene Expression Profile Identifies Tyrosine Kinase c-Met as a Targetable Mediator of Antiangiogenic Therapy Resistance , 2013, Clinical Cancer Research.

[21]  T. Golub,et al.  Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion , 2012, Nature.

[22]  T. Golub,et al.  Tumor microenvironment induces innate RAF-inhibitor resistance through HGF secretion , 2012, Nature.

[23]  T. Nakagawa,et al.  Met Kinase Inhibitor E7050 Reverses Three Different Mechanisms of Hepatocyte Growth Factor–Induced Tyrosine Kinase Inhibitor Resistance in EGFR Mutant Lung Cancer , 2012, Clinical Cancer Research.

[24]  F. Hirsch,et al.  Hepatocyte growth factor expression in EGFR-mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  G. Watanabe,et al.  Crosstalk to Stromal Fibroblasts Induces Resistance of Lung Cancer to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors , 2009, Clinical Cancer Research.

[26]  Amy McKee,et al.  On Trk—The TrkB Signal Transduction Pathway Is an Increasingly Important Target in Cancer Biology , 2009, Clinical Cancer Research.

[27]  K. Carraway,et al.  Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells. , 2008, Cancer research.

[28]  Toshikazu Nakamura,et al.  Hepatocyte growth factor and the Met system as a mediator of tumor–stromal interactions , 2006, International journal of cancer.

[29]  A. Joe,et al.  Mechanisms of Disease: oncogene addiction—a rationale for molecular targeting in cancer therapy , 2006, Nature Clinical Practice Oncology.

[30]  H. Moses,et al.  Stromal fibroblasts in cancer initiation and progression , 2004, Nature.

[31]  A. Tsao,et al.  ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers , 2012 .

[32]  A. Joe,et al.  Oncogene addiction. , 2008, Cancer research.