Resistance to chemotherapeutic and targeted anticancer drugs is one of the major causes for the lethal cancer progression. Genetic alterations (point mutations, amplifications and deletions) in the genomic DNA are the major causes of the both intrinsic and acquired resistance. Genome-wide CRISPR screens allow us to create a population of cells with single deletions covering whole human genome. Using cancer cell lines of different origin and current cancer treatments we perform resistance and sensitivity screens. This lets us to uncover the pathways which lead to cancer drug resistance, cancer sensitivity and understand better biology of cancer cells.