Histone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective

Abstract

The development and immune evasion of cancer stem cells (CSCs) limit the efficacy of currently available anticancer therapies. Recent studies have shown that epigenetic reprogramming regulates the expression of characteristic marker proteins and tumor plasticity associated with cancer cell survival and metastasis in CSCs. CSCs also possess unique mechanisms to evade external attacks by immune cells. Hence, the development of new strategies to restore dysregulated histone modifications to overcome cancer resistance to chemotherapy and immunotherapy has recently attracted attention. Restoring abnormal histone modifications can be an effective anticancer strategy to increase the therapeutic effect of conventional chemotherapeutic and immunotherapeutic drugs by weakening CSCs or by rendering them in a naive state with increased sensitivity to immune responses. In this review, we summarize recent findings regarding the role of histone modifiers in the development of drug-resistant cancer cells from the perspectives of CSCs and immune evasion. In addition, we discuss attempts to combine currently available histone modification inhibitors with conventional chemotherapy or immunotherapy. Cancer drug resistance: Preventing modification of chromatin proteinsUnderstanding how modification of histones, structural proteins that support chromatin and affect gene expression, helps cancer stem cells interact with immune cells will help fight drug-resistant cancers. An important mechanism of cancer treatment resistance is histone modification. Ming Li Jin and Kwang Won Jeong at Gachon University in Incheon, South Korea, reviewed recent research into histone modifications in drug-resistant cancers. Much is known about how histone-modifying enzymes remodel the tumor micro-environment, allowing cancer stem cells to proliferate and block immune cell activity. Drugs that inhibit histone-modifying enzymes show great promise, but it is difficult to identify the precise mechanisms involved. Research should also address why inhibitors are less effective in some cancers, and how a patient's unique tumor micro-environment could be analyzed to provide personalized precision medicine.