Abstract
•Tumor heterogeneity is the root cause of tumor plasticity and treatment resistance.•Cancer stem cells are the seed cells for heterogenic progression in tumor mass.•Epigenetic modifications are a major contributor to the heterogenic tumor.•Redox imbalance-driven epigenetic modulations to influence tumor heterogeneity.•Epidrugs are emerging as adjunct therapy against tumor heterogeneity.
“Heterogeneity” in tumor mass has immense importance in cancer progression and therapy. The impact of tumor heterogeneity is an emerging field and not yet fully explored. Tumor heterogeneity is mainly considered as intra-tumor heterogeneity and inter-tumor heterogeneity based on their origin. Intra-tumor heterogeneity refers to the discrepancy within the same cancer mass while inter-tumor heterogeneity refers to the discrepancy between different patients having the same tumor type. Both of these heterogeneity types lead to variation in the histopathological as well as clinical properties of the cancer mass which drives disease resistance towards therapeutic approaches. Cancer stem cells (CSCs) act as pinnacle progenitors for heterogeneity development along with various other genetic and epigenetic parameters that are regulating this process. In recent times epigenetic factors are one of the most studied parameters that drive oxidative stress pathways essential during cancer progression. These epigenetic changes are modulated by various epidrugs and have an impact on tumor heterogeneity. The present review summarizes various aspects of epigenetic regulation in the tumor microenvironment, oxidative stress, and progression towards tumor heterogeneity that creates complications during cancer treatment. This review also explores the possible role of epidrugs in regulating tumor heterogeneity and personalized therapy against drug resistance.