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Yang Shi’s group identify two transcriptional co-activators that are selectively important for cancer cell but not normal cell survival.

A good cancer drug should selectively kill cancer cells while leaving healthy, normal cells relatively untouched to reduce treatment side-effects. In order to achieve this selectivity, one strategy is to target genes that are essential for cancer cell survival but not for normal cells.

The DepMap project has developed a method to define these selectively essential genes in cancer cells. However, it is challenging to manually sort which genes to investigate further, out of the long list generated.

In this paper published in Cell Discovery, Chen Zhou and colleagues from Ludwig Oxford’s Yang Shi’s group developed a strategy to rank the selectively essential genes according to how much is known about each one, enabling prioritisation of previously understudied potential targets. This method identified several novel targets, including C11orf53 and COLCA2 in tuft cell-like small-cell lung cancer (SCLC).

The team generated biochemical and functional data which supports the importance of these genes for tuft-cell SCLC via their function as a co-activator for the POU2F3 transcriptional regulator. Further, work from others demonstrate that mice are viable without C11orf53 or COLCA2, indicating the selectively of the requirement for these genes in cancer but not normal biological processes.

These findings agree with two other reports of the role of these genes in SCLC that came out during the work. The Ludwig Oxford team also noted that C11orf53 and COLCA2 are overexpressed in tumour samples from other cancers, indicating a potential role in a wider range of cancer types.

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Ludwig Oxford Professor Yang Shi has been elected as a Fellow of the Royal Society for his contributions to epigenetics research