Brain penetration and efficacy of tepotinib in orthotopic patient-derived xenograft models of MET-driven non-small cell lung cancer brain metastases

Friese-Hamim, Manja; Clark, Anderson; Perrin, Dominique; Crowley, Lindsey; Reusch, Christof; Bogatyrova, Olga; Zhang, Hong; Crandall, Timothy; Lin, Jing; Ma, Jun; Bachner, David; Schmidt, Jürgen; Sameš, Martin; Stroh, Christopher

doi:10.1016/j.lungcan.2021.11.020

Cited by 14 publications

(19 citation statements)

References 46 publications

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“…In addition, proto-oncogene MET mutation induce cancer cell invasion and tepotinib, a MET inhibitor has been approved for the treatment of metastatic MET ex14 skipping NSCLC with a durable response [29–31]. A BM mouse model established by intracranial injection of patient-derived cancer cells (LU5349 and LU5406) has demonstrated that tepotinib compared to control group promotes tumor regression [32 ▪ ]. This result provides support for the intracranial activity of tepotinib in regard of the data of case report [33].…”

Section: Preclinical Model For Drug Development In Brain Metastasesmentioning

confidence: 66%

Preclinical models to understand the biology and to discover new targets in brain metastases

Kindt

Kotecki

Awada

2023

Current Opinion in Oncology

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Purpose of review Incidence of brain metastases increases overtime therefore it is important to rapidly progress in the discovery of new strategies of treatment for these patients. In consequence, more and more preclinical models of brain metastases (BM) are established to study new treatments for melanoma, lung, and breast cancer BM. Here, we reviewed the most recent findings of new drugs assessed in BM mouse preclinical models. Recent findings BM are a common metastatic site of several types of solid cancers and can be difficult to treat due to the unique environment of the brain and the blood-brain barrier. Currently, several preclinical models of BM have been demonstrated that new molecular targeted therapies, small metabolic inhibitors, immunotherapies or a combination of these drugs with radiotherapy lead to a reduction of BM growth and an improvement of mouse survival. Summary The use of preclinical models of BM is crucial to discover new treatment strategies for patients with BM. In the last years, some new drugs have been highlighted in preclinical models and are now tested in clinical trials including patients with brain metastases.

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Section: Preclinical Model For Drug Development In Brain Metastasesmentioning

confidence: 66%

Preclinical models to understand the biology and to discover new targets in brain metastases

Kindt

Kotecki

Awada

2023

Current Opinion in Oncology

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“…e 90% death of non-small-cell lung cancer (NSCLC) patients is primarily due to metastases, which are poorly amenable to therapeutic intervention [60]. Many studies have shown orthotopic engraftment of human NSCLC tumors in mice for the studies of metastasis [61][62][63][64][65].…”

Section: Orthotopic Modelmentioning

confidence: 99%

Research Status of Mouse Models for Non-Small-Cell Lung Cancer (NSCLC) and Antitumor Therapy of Traditional Chinese Medicine (TCM) in Mouse Models

Chen¹,

Zheng

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Non-small-cell lung cancer (NSCLC) is known as one of the most lethal cancers, causing more than 1 million deaths annually worldwide. Therefore, the development of novel therapeutic drugs for NSCLC has become an urgent need. Herein, various mouse models provide great convenience not only for researchers but also for the development of antitumor drug. Meanwhile, TCM, as a valuable and largely untapped resource pool for modern medicine, provides research resources for the treatment of various diseases. Until now, cell-derived xenograft (CDX) model, patient-derived xenograft (PDX) model, syngeneic model, orthotopic model, humanized mouse model (HIS), and genetically engineered mouse models (GEMMs) have been reported in TCM evaluation. This review shows the role and current status of kinds of mouse models in antitumor research and summarizes the application progress of TCM including extracts, formulas, and isolated single molecules for NSCLC therapy in various mouse models; more importantly, it provides a theoretical exploration of what kind of mouse models is ideal for TCM efficacy evaluation in future. However, there are still huge challenges and limitations in the development of mouse models specifically for the TCM research, and none of the available models are perfectly matching the characteristics of TCM, which suppress the tumor growth through various mechanisms, especially by regulating immune function. Nevertheless, with fully functional immune system existing in syngeneic model and humanized mouse model (HIS), it is still suggested that these two models are more suitable for development of TCM especially for TCM extracts or formulas. Moreover, continued efforts are needed to generate more reliable mouse models to test TCM formulas in future research.

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“… 22 , 23 In preclinical models of NSCLC with MET amplification, tepotinib induced complete regression of cell-line- and patient-derived xenografts, including after orthotopic implantation in the brain. 24 , 25 In addition, antitumor activity has also been observed with tepotinib plus gefitinib or osimertinib in patients with epidermal growth factor receptor ( EGFR )-mutant NSCLC and MET amplification. 26 , 27 , 28 …”

Section: Introductionmentioning

confidence: 99%

Brain penetration and efficacy of tepotinib in orthotopic patient-derived xenograft models of MET-driven non-small cell lung cancer brain metastases

Cited by 14 publications

References 46 publications

Preclinical models to understand the biology and to discover new targets in brain metastases

Preclinical models to understand the biology and to discover new targets in brain metastases

Research Status of Mouse Models for Non-Small-Cell Lung Cancer (NSCLC) and Antitumor Therapy of Traditional Chinese Medicine (TCM) in Mouse Models

Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B

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