Epigenetic Mechanisms of Metal Carcinogenicity: Exploring Associated Therapeutic Options for Individualised Treatments

Abstract

While naturally occurring, heavy metals pose a significant global public health risk due to their extensive utilisation in industrial, residential, and agricultural activities, impacting the health of millions worldwide. Occupational and environmental exposure to these metals through contaminated sources affects organs, including the development of cancer. Arsenic, chromium, nickel, and cadmium, among others, have been classified by the International Agency for Research on Cancer (IARC) as Group 1 carcinogens, indicating a strong association with various types of cancer. Cancer ranks as the second leading cause of death globally, with an estimated 9.6 million deaths attributed to it. Numerous mechanisms contribute to heavy metal-induced carcinogenesis, including oxidative stress, DNA damage, and aberrant signalling transduction pathways. Recent advancements in understanding epigenetics have unveiled the role of epigenetic alterations in cancer development. Epigenetic alterations are functionally relevant modifications which affect gene expression but do not change the DNA sequence. Two primary epigenetic mechanisms—histone modification and non-coding RNA (ncRNA)-are associated with gene silencing and DNA methylation, which are pivotal in regulating gene expression and cell differentiation. Alterations in these epigenetic patterns contribute to metal-induced carcinogenicity by rendering tumour suppressor genes inactive while activating anti-apoptotic and pro-proliferative genes. Understanding the underlying epigenetic mechanisms of heavy metals holds promise for guiding future research and developing targeted therapeutic interventions. Various inhibitors, including DNA methylation inhibitors (DNMTIs), histone modification inhibitors (HMIs), histone deacetylase inhibitors (HDACIs), histone methyltransferase inhibitors, and non-coding RNA-targeted therapies, offer avenues for interfering with these mechanisms, thereby positively impacting the treatment of metal-induced cancers, mainly through individualised treatment approaches.