A research team led by Prof. LIN Wenchu, a senior fellow of High Magnetic Field Laboratory, Chinese Academy of Sciences (CHMFL) has revealed that combination treatment of two small molecules (JQ1 and ABT-263) effectively kills MYCN-amplified small cell lung cancer (SCLC).

SCLC is the most aggressive subtype of lung cancer accounting for 10~15% of the total lung cancer cases. Unlike non-small cell lung cancer (NSCLC), the rare occurrences of druggable oncogenes or kinases make SCLC difficult to be harnessed for precision treatment.

Previous studies have shown that amplification of MYC family genes and overexpression of Bcl-2 protein are common in SCLC, and they are likely therapeutic targets for SCLC.

In this study, Mr. WANG Huogang and Dr. HONG Bo of LIN's team demonstrated for the first time that co-targeting of N-Myc and Bcl-2 resulted in marked synergistic antitumor effects in MYCN-amplified SCLC.

They found that MYCN-amplified SCLC cells were highly sensitive to a Bromodomain and Extra-Terminal domain (BET) inhibitor JQ1, which was able to inhibit N-Myc protein expression.

The inhibition of N-Myc by JQ1 induced the expression of Bim, and thereby sensitizing MYCN-amplified SCLC cells to ABT-263. ABT-263 and JQ1 co-treatment in MYCN-amplified SCLC cells markedly disrupted Bim/Bcl-2 interaction, and prevented Bim’s interaction with Mcl-1.

Importantly, this JQ1/ABT-263 co-targeting substantially inhibited the growth of MYCN-amplified SCLC xenografts in vivo.

In summary, the study demonstrates a new JQ-1/ABT-263 co-targeting strategy that can be employed for MYCN-amplified SCLC with high efficacy.

The findings have been published online in Oncotarget entitled "JQ1 synergizes with the Bcl-2 inhibitor ABT-263 against MYCN-amplified small cell lung cancer".

This investigation was supported by National Natural Science Foundation of China, Natural Science Foundation of Anhui Province, and the 100-Talent Program of the Chinese Academy of Sciences.