KEY TAKEAWAYS
- The study aimed to develop medium-scale optical drug screening to identify synergistic combinations and analyze individual drug interactions in NSCLC cell line.
- Results demonstrated the optical drug screening’s efficacy in identifying synergistic combinations and revealing individual drug interactions in NSCLC.
Resistance to cancer therapy is a significant obstacle in achieving successful treatment outcomes, particularly in non-small cell lung cancer (NSCLC). Combinatorial therapy involving multiple drugs is often employed to counteract drug resistance, with the aim of enhancing efficacy and minimizing side effects. Identifying synergistic drug combinations, which can effectively target cancer cells at lower doses, holds promise for improving patient prognosis.
Previous studies have tackled this challenge using various methods, from small-scale targeted assays to large-scale growth assays. However, the sheer number of possible combinations has posed technical hurdles to these efforts.
In this study, Sijiao Wang and the team conducted a medium-scale optical drug synergy screening using a NSCLC cell line. They delved deeper into individual drug interactions within these combinations through high-content image analysis. Optical high-content analysis of cellular responses has emerged as a valuable tool in drug discovery, functional genomics, and toxicology research. Leveraging this approach, they aimed to shed light on the complex dynamics of combinatorial drug responses in cancer treatment.
The results demonstrated that through exhaustive examination of all possible combinations of 12 drug compounds across six distinct drug classes—including mTOR inhibitors, HDAC inhibitors, HSP90 inhibitors, MT inhibitors, DNA inhibitors, and proteasome inhibitors.
Researchers successfully identified synergistic interactions between INK128, an mTOR inhibitor, and HDAC inhibitors. This finding was consistent with similar observations reported elsewhere.
The high-content analysis further revealed that HDAC inhibitors, HSP90 inhibitors, and proteasome inhibitors played pivotal roles in shaping combinatorial drug responses when combined with MT inhibitors, DNA inhibitors, or mTOR inhibitors. This suggested that less dominant drugs may have reduced priority as constituents of multidrug cocktails.
The optical drug screening platform effectively pinpointed synergistic drug combinations within a NSCLC cell line. Moreover, the high-content analysis provided insights into the interplay between individual drugs within the mix, elucidating the mechanisms underlying combinatorial drug responses.
Funding for this research is provided by New York University at Shanghai, the NYU-ECNU Center for Computational Chemistry at NYU Shanghai, and the National Science Foundation of China.
Source: https://pubmed.ncbi.nlm.nih.gov/38475728/
Wang S, Oliveira-Silveira J, Fang G, et al. (2024) “High-content analysis identified synergistic drug interactions between INK128, an mTOR inhibitor, and HDAC inhibitors in a non-small cell lung cancer cell line.” BMC Cancer. 2024 Mar 12;24(1):335. doi: 10.1186/s12885-024-12057-4. PMID: 38475728.
