Abstract
Despite the numerous investigations on resistance mechanisms, drug resistance in cancer therapies still limits favorable outcomes in cancer patients. The complexities of the inherent characteristics of tumors, such as tumor heterogeneity and the complicated interaction within the tumor microenvironment, still hinder efforts to overcome drug resistance in cancer cells, requiring innovative approaches. In this review, we describe recent studies offering evidence for the essential roles of amino acid metabolism in driving drug resistance in cancer cells. Amino acids support cancer cells in counteracting therapies by maintaining redox homeostasis, sustaining biosynthetic processes, regulating epigenetic modification, and providing metabolic intermediates for energy generation. In addition, amino acid metabolism impacts anticancer immune responses, creating an immunosuppressive or immunoeffective microenvironment. A comprehensive understanding of amino acid metabolism as it relates to therapeutic resistance mechanisms will improve anticancer therapeutic strategies.
Highlights
Many advances in cancer treatments have been made, the occurrence of drug resistance in cancer cells remains a challenge
Metabolic alterations must occur to meet the diverse metabolic needs required for adaptation to anticancer drugs and cancer cell proliferation, metabolic reprogramming in response to anticancer drug therapies has been considered a bystander effect of biological processes induced by drugs rather than a cause of drug resistance
We introduce the amino acid-driven drug resistance mechanism in tumors and highlight amino acid-dependent vulnerabilities in cancer cells that can be leveraged to improve anticancer drug therapies
Summary
Many advances in cancer treatments have been made, the occurrence of drug resistance in cancer cells remains a challenge. Chemotherapies, targeted therapies, and immunotherapies have been effectively used as tumor treatments, whereas the emergence of drug-resistant clones leads to distant metastasis and repopulation of cancer cells, restricting clinical outcomes. Several recent studies have demonstrated that drug-specific therapeutic pressure leads to metabolic reprogramming, driving drug resistance in cancer cells [3,4]. We introduce the amino acid-driven drug resistance mechanism in tumors and highlight amino acid-dependent vulnerabilities in cancer cells that can be leveraged to improve anticancer drug therapies. We aim to describe the mechanisms underlying cancer drug resistance with respect to amino acid metabolism and anticipate future directions that can be exploited to improve drug therapy in cancer patients.
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