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Drug Resistance in Cancer Therapy and the Role of Epigenetics
Department of Pediatrics, Nippon Medical School, Tokyo, Japan
Effective leukemia treatment is seriously hampered by drug resistance, and the potential role of epigenetic mechanisms in cancer drug resistance has recently been investigated. With conventional anticancer drugs, including alkylating drugs, anti-metabolite drugs, topoisomerase inhibitors, and microtubule inhibitors-which have been available for half a century-drug resistance often develops because of decreased expression of target enzymes, in conjunction with increased expression of drug export pumps. Alterations of target gene expression and increased export pump function might be caused by epigenetic changes, such as alterations in methylation status, as well as by changes in histone acetylation status. In addition, newly developed anticancer drugs, including small-molecule drugs, such as kinase inhibitors, antibody drugs, and immune modulatory drugs, also resulted in development of drug resistance within 1 year, although these drugs showed significant effectiveness for patients resistant to conventional anticancer drugs. The resistant cells exhibited increased expression of bypass pathways, activation of downstream cascades, decreased expression of antigens of tumor cells, increased DNA repair activity, and increased expression of drug export pumps, which also suggests the presence of epigenetic changes. This article reviews drug resistance in cancer therapy and the possible roles of epigenetic mechanisms.
J Nippon Med Sch 2020; 87: 244-251
Keywords
leukemia, drug resistance, epigenetics
Correspondence to
Takeshi Asano, M.D., Department of Pediatrics, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba 270-1694, Japan
july1364@nms.ac.jp
Received, April 23, 2019
Accepted, May 1, 2020
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