Small cell lung cancer is the most malignant subtype of lung cancer, accounting for about 15% to 20% of lung cancer patients. Unlike non-small cell lung cancer, there are currently no effective targeted therapies for the treatment of small-cell lung cancer due to the fact that targeted therapeutics such as EGFR and ALK are rare in small cell lung cancer. This study found an effective targeted therapy for small cell lung cancer with N-MYC amplification: synergistic inhibition of N-MYC-expanded small cells by the combination of two small molecule inhibitors (JQ1 and ABT-263) Lung cancer growth.

       The team found that the N-MYC-expanded small cell lung cancer cell line is sensitive to the epigenetic drug, the PET bromodomain inhibitor, JQ1. They found that JQ1 is more sensitive to the BCL-2 inhibitor ABT-263 by inhibiting the expression of BIM protein by N-MYC, thereby enabling N-MYC-expanded small cell lung cancer cells. The combined treatment of JQ1 and ABT-263 effectively interferes with the binding of BIM to BCL-2 and MCL-1, thereby allowing BIM to function to induce apoptosis. Researchers further demonstrated that the combination of JQ1 and ABT-263 effectively inhibits the growth of N-MYC-expanded small cell lung cancer xenografts in a mouse model of small cell lung cancer xenografts. Research work shows that the combined use of JQ1 and ABT-263 may be an effective method for the treatment of N-MYC-amplified small cell lung cancer with potential clinical value.

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       Wang H, Hong B, Li X, et al. JQ1 synergizes with the Bcl-2 inhibitor ABT-263 against MYCN-amplified small cell lung cancer[J]. Oncotarget, 2017.