Anti-Tumor Drug Resistance and Modern Oncologic Pharmaco-Therapy: RNA and DNA Methylation, Mechanisms and Histone Modification, Epigenetic Regulation and Targeting Epigenetic Modifiers in Contemporary Cancer Therapy

Abstract

Metastasis, the spread of cancer cells from the primary tumor to the surrounding tissues and to distant organs, is one (and perhaps the primary) of the major causes of cancer-related death (or cancer morbidity and mortality). Indeed, it is estimated that metastasis is responsible for about 90% of cancer deaths. The major factors contributing to the metastasis of cancer cells are epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Herein, the cancer cells must detach from the primary tumor, intravasate into the circulatory and lymphatic systems, evade immune attack, extravasate at distant capillary beds, and invade and proliferate in distant organs. Accruing evidence suggests that the malfunction of epigenetic regulation in the functioning of a gene is directly related to the generation of tumors and cancer. Henceforth, the potential and capacity to change or re-program the epigenetic landscape within the epigenome of cancer is possibly the most promising and pursued targeted therapy, nowadays. Such would lead to reversing drug resistance and so, new therapeutic modalities. Indeed, contemporary oncologic pharmaco-therapy for cancer has and continues to undergo remarkable changes; especially lately, in terms of the introduction of effective cancer-specific molecular-targeted therapeutic agents. This introductory chapter to the book titled: “DNA Replication – Mechanisms, Epigenetics, and Gene Therapy Applications” discusses DNA and RNA methylation, the mechanisms of histone modification, and presents a variety of epigenetic modifications which can lead to anti-tumor drug resistance. It also explores how targeting epigenetic modifiers can reverse drug resistance.