The paper provides an overview of the mechanisms that promote drug resistance in cancer, including drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and epithelial-mesenchymal transition (EMT). It also discusses the role of inherent tumor cell heterogeneity and epigenetic modifications in drug resistance. The authors highlight the importance of understanding these mechanisms to develop effective treatments and prevent the formation of drug-resistant cancers. They emphasize the potential of epigenetic therapies, such as histone deacetylase inhibitors (HDACi), to sensitize cancer cells to conventional and targeted therapies. The paper concludes by discussing the best treatment options for drug-resistant cancers and future research directions.The paper provides an overview of the mechanisms that promote drug resistance in cancer, including drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and epithelial-mesenchymal transition (EMT). It also discusses the role of inherent tumor cell heterogeneity and epigenetic modifications in drug resistance. The authors highlight the importance of understanding these mechanisms to develop effective treatments and prevent the formation of drug-resistant cancers. They emphasize the potential of epigenetic therapies, such as histone deacetylase inhibitors (HDACi), to sensitize cancer cells to conventional and targeted therapies. The paper concludes by discussing the best treatment options for drug-resistant cancers and future research directions.