Pooled Phenotypic CRISPR Screening Enables the Identification of Synergistic Drug Combinations for Cancer Therapy

Single agent therapies have often limited clinical benefit, therefore identifying targets that synergize with a given drug is crucial for identifying combination therapy approaches that can maximize treatment efficiency. Cancer drugs, such as Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors, often lead to proliferative arrest rather than cell death, leaving a reservoir of live tumor cells, some of which might be resistant to the drug or lead to the development of drug resistance. Identifying targets that can induce cell death under these circumstances could be used to eliminate cancer cells and to prevent or delay the development of drug resistance.