Cancer versus non-cancer dependencies

I found very important to know which genes are essential for cancer growth, or which compounds might kill cancer cells in order to find new therapies. But imagine that treating with a compound might also kill normal cells, from same or different tissue/organ. Is there any way to see that using a compound might not affect non-cancer cells while selectively reducing viability of a type of cancer? Is there any way a knocking-down a certain gene might not affect non-cancer cells while killing cancer cells? I’m thinking in a gene therapy approach targeted to disrupt genes which are needed in the cancer contex and not in the non-cancer (normal) cell context.

Generally, we look for the selectivity of a dependency within cancer cell lines, on the assumption that it’s not very likely for a gene to be a dependency in all cancers and only cancers. The gene’s page will indicate whether it appears to be selective. Forthcoming tools will provide more sophisticated ways of addressing this question with DepMap data. You can also check other sources like gnomAD to get some idea of the gene’s importance for human health.

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This is a very good but difficult question. We expect that genes or compounds that preferentially kill cancer cells will have a selective profile in the depmap data (e.g. kill only a subset of the cells). However, just because a gene or compound has a selective profile doesn’t mean it will be selective to cancer cells. For example, a gene essential in a specific type of lung normal cells could have a selective dependency profile but be too toxic if suppressed in patients. This is why using the genetic and molecular information of the cell lines to understand WHY the cells are sensitive is critical to identify cancer vulnerabilities.

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