Abstract: Increased understanding of cancer genome is affecting every corner of cancer research. Although human tumor cell lines have been used as essential tools for decades, there are only a few cell line panels have been developed for the drug screening. There is a gap between the new knowledge of cancer genome and the cell line based platforms for both basic and translational research. Here, we show that new generation tumor cell panels are filling the gap. The panels were generated by selecting authenticated cell lines derived from variant cancer types, and annotated with genetic alteration information generated by large scale sequencing projects such as the Catalog of Somatic Mutations in Cancer (COSMIC) and the Cancer Cell Line Encyclopedia (CCLE). To capture the genetic diversity of cancer, each panel includes cell lines with varying gene mutation complexity. To further facilitate targeted drug discovery, the molecular signature tumor cell line panels focus on individual driver genes, critical protein kinases, transcription factors and cell signaling pathways. Those panels have been analyzed to verify gene mutation, gene expression, protein expression and bio-functions.