EZH2 Inhibition and Cisplatin as a Combination Anticancer Therapy: An Overview of Preclinical Studies

SIMPLE SUMMARY: Cisplatin is a chemotherapy drug widely used in the treatment of different cancer types. However, cisplatin displays a high range of toxicity and its use usually leads to resistance. Therefore, combination therapies that include cisplatin are explored to alleviate the problems that are elicited by cisplatin use. EZH2 is an epigenetic regulator with an increased expression and activity in many cancer types, which, in general, potentiates cancer growth and expansion. In the past decade, many EZH2 inhibitors were introduced and investigated for their anticancer properties. In this review paper, we explore the work that analyzed the joint action of EZH2 inhibitors and cisplatin in different tumor types. We found that combination therapy of EZH2 inhibitors and cisplatin could potentially be beneficial for the treatment of lung, ovarian, and breast cancers. However, in testicular germ cell tumors, according to the published data, such a combination could potentially have antagonistic effects. ABSTRACT: Anticancer monotherapies are often insufficient in eradicating cancer cells because cancers are driven by changes in numerous genes and pathways. Combination anticancer therapies which aim to target several cancer traits at once represent a substantial improvement in anticancer treatment. Cisplatin is a conventional chemotherapy agent widely used in the treatment of different cancer types. However, the shortcomings of cisplatin use include its toxicity and development of resistance. Therefore, from early on, combination therapies that include cisplatin were considered and used in a variety of cancers. EZH2, an epigenetic regulator, is frequently upregulated in cancers which, in general, potentiates cancer cell malignant behavior. In the past decade, numerous EZH2 inhibitors have been explored for their anticancer properties. In this overview, we present the studies that discuss the joint action of cisplatin and EZH2 inhibitors. According to the data presented, the use of cisplatin and EZH2 inhibitors may be beneficial in the treatment of lung, ovarian, and breast cancers, since there is a substantial amount of published evidence that suggests their concerted action. However, in testicular germ cell tumors, such a combination would not be recommended because cisplatin resistance seems to be associated with decreased expression of EZH2 in this tumor type.