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  • Nintedanib found...

Nintedanib found effective for drug resistant gastrointestinal stromal tumors

Dr. Kamal Kant KohliWritten by Dr. Kamal Kant Kohli Published On 2022-04-15T19:30:15+05:30  |  Updated On 15 April 2022 2:02 PM GMT
Nintedanib found effective for drug resistant gastrointestinal stromal tumors
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Nintedanib could be used in the treatment of drug-resistant gastrointestinal stromal tumors (GISTs), finds a research led by Prof. LIU Qingsong and LIU Jing from the Hefei Institutes of Physical Science (HFIPS) of the Chinese Academy of Sciences (CAS)Results of the research were published on Molecular Oncology.Nintedanib is a multikinase inhibitor of the receptor tyrosine kinase...

Nintedanib could be used in the treatment of drug-resistant gastrointestinal stromal tumors (GISTs), finds a research led by Prof. LIU Qingsong and LIU Jing from the Hefei Institutes of Physical Science (HFIPS) of the Chinese Academy of Sciences (CAS)

Results of the research were published on Molecular Oncology.

Nintedanib is a multikinase inhibitor of the receptor tyrosine kinase FGFR/VEGFR/PDGFR. GISTs are mesenchymal tumors that usually occur in the gastrointestinal tract. Nearly 85% of GISTs bear oncogenic mutations in mast/stem cell growth factor receptor (KIT). As the first-line therapy, imatinib has significantly improves GIST patient survival. However, most patients eventually experience disease progression due to KIT secondary mutations. Besides, activation of alternative signaling pathways may also lead to drug resistance.

Although several second- and third-generation KIT kinase inhibitors could overcome some of the KIT mutations conferring resistance, the low clinical responses and narrow safety window have limited their broad application. Therefore, there is still an urgent need for effective drugs to overcome the problem.

In this study, through high-throughput screening, the research team found that nintedanib, which has been approved for the treatment of idiopathic pulmonary fibrosis and non-small-cell lung cancer, exhibited strong inhibitory effects against a panel of primary gain-of function mutations and secondary drug resistance mutations of KIT kinase, especially the T670I mutation.

In vitro experiments showed that nintedanib significantly inhibited the proliferation of GIST cell lines and human primary GIST cells through the KIT signaling pathway.

In addition, they found that nintedanib overcame resistance mediated by extracellular signal-regulated kinase reactivation caused by upregations of fibroblast growth factor activity. In vivo antitumor efficacy has also been observed in several xenograft GIST models.  

To read the full article, click on the following link:

10.1002/1878-0261.13199

Molecular Oncologytumorsstromal tumorsnintedanibfibrosiscancercancer patientscancer treatmentpulmonary fibrosis
Source : Molecular Oncology
Dr. Kamal Kant Kohli
Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Before Joining Medical Dialogues, he has served at important positions in the medical industry in India including as the Hony. Secretary of the Delhi Medical Association as well as the chairman of Anti-Quackery Committee in Delhi and worked with other Medical Councils in India. Email: editorial@medicaldialogues.in. Contact no. 011-43720751

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