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Acquisition of Resistance to MTI‐101 Selects for Favorable MET phenotype in Lung Cancer
Author(s) -
Jones Clark
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02905
Subject(s) - lung cancer , osimertinib , cancer , medicine , phenotype , drug resistance , cancer research , drug , acquired resistance , cancer cell , biology , bioinformatics , pharmacology , oncology , adenocarcinoma , genetics , gene , ros1
Lung cancer has a high mutational burden and therefore, individualized therapies often prove to be most effective. The biggest obstacle is the development of resistance to these therapies. MTI‐101 is a novel cancer therapeutic drug that has been shown to be effective in treatment of multiple cancers including prostate, multiple myeloma and lung cancer. Further analysis of MTI‐101's effect on lung cancer could give insight to its mechanism of action. Two independent isogenic cell lines were created to analyze what leads to MTI‐101 resistance. By comparing the Wild type and drug resistant lines derived from the same parent, a better understanding can be gained as to genotypic and phenotypic selection of MTI‐101. Resistance to the drug illustrated the development of a reverse EMT phenotype. MTI‐101 selects for cells with increased RNA and protein levels of E‐cadherin, decreased vimentin, along with decreased migration and invasion capacity. It was also found that MTI‐101 shows synergistic effects when combined with Osimertinib in EGFR driven cell lines. In addition, the cells MTI‐101 selects for are more sensitive to Osimertinib as a single agent than the respective wild type. Therefore, this is a novel finding that MTI‐101 selects for a less fit and less aggressive phenotype that proves more sensitive to current FDA approved drugs for lung cancer.