Cancer cells can acquire resistance to targeted drugs or chemotherapy drugs by several mechanisms. Several mutations, mainly pathogenic single nucleotide polymorphisms (SNPs), are known to develop during the course of therapy conferring resistance to cancer cells. One such example is the T315I mutation in the BCR-ABL kinase domain (threonine is substituted to isoleucine) which confers resistance against imatinib, a tyrosine kinase inhibitor used in treatment of BCR-ABL positive hematological cancers. At the protein level, the mutation T315I results in a loss of a hydrogen bond, which is necessary for the binding of imatinib to the ATP-binding site of BCR-ABL, leading to significant reduction in efficacy of the drug. CRISPR based editing offers novel approach to silence such mutations and thereby restore drug efficacy. EGFR T790M and TP53 R273H mutations are associated with gefitinib (a tyrosine kinase inhibitor drug) resistance in lung cancer patients. Yoon et al. showed that co-delivery of adenine base editor (ABE) and EGFR-and TP53-SNP specific sgRNA via adenovirus resulted in accurate correction of the oncogenic mutations with high efficiency in vitro and in vivo. There was increased drug sensitivity and suppressed abnormal tumor growth in cells with altered EGFR and TP53 mutations as compared to control cells. In breast cancer cells, there are studies done which show that genetically modified T47D and MCF7 breast cancer cells containing mutations in estrogen receptor 1 (ESR1) (Y537S and D538G) showed estrogen-independent growth and resistance to fulvestrant, raloxifene and 4hydroxytamoxifen (4-OHT) in vitro. In addition to addressing existing drug resistances, CRISPR can also be used to identify newer drug resistance mechanisms and mutations. Chen et al. showed that, in triple negative breast cancer cells (HCC1937) the genetic ablation of ATPE1, a base excision repair enzyme led to resistance to olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor. In another study, CRISPR based knockout of MAP3K1 in mutant PIK3CA breast cancer cells increased the proliferation rate and decreased sensitivity to AZD5363 (an AKT inhibitor) in vitro as well as in vivo. 221