Insights into the therapeutic potential of histone deacetylase inhibitor/immunotherapy combination regimens in solid tumors

Solid tumors including skin, lung, breast, colon, and prostate cancers comprise the most diagnosed cancers worldwide. Treatment of such cancers is still challenging specially in the advanced/metastatic setting. The growing understanding of the tumor microenvironment has revolutionized the cancer therapy paradigms. Targeting programmed death-1 (PD-1)/PD-L1 immune checkpoint has been extensively studied over this decade as a new trend in the management of hard-to-treat cancers by harnessing the power of the immune system to eradicate the tumors. Yet, low response rate and resistance were observed when immunotherapies were tested as monotherapy. This urged the need to develop combinatorial regimens of immunotherapy with other immune modulatory agents to enhance its therapeutic potential and help in reverting the resistance. Epigenetic modifiers such as histone deacetylase inhibitors (HDACIs) showed favorable effects on modulating the tumor microenvironment along with the host immune cells. This qualified HDACIs as an attractive candidate class to be tested in combination with immunotherapy. In this review we cover the ongoing clinical trials that investigate the safety and/or the efficacy of HDACI/immunotherapy combinations in solid tumors including skin cancer, prostate cancer, breast cancer, colorectal cancer, lung cancer and recapitulates areas for future research.

Automated summary

Solid tumors, such as skin, lung, breast, colon, and prostate cancers, pose a significant challenge in treatment, especially in advanced/metastatic cases. Targeting the PD-1/PD-L1 immune checkpoint has been studied extensively as a new approach to managing these hard-to-treat cancers. However, monotherapy with immunotherapies has shown low response rates and resistance, necessitating the development of combination regimens with other immune modulatory agents. Epigenetic modifiers, such as HDACIs, have shown promising effects in modulating the tumor microenvironment and host immune cells, making them attractive candidates for combination testing with immunotherapy.