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

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Abstract

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.

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Acknowledgements

MFT is supported by L’Oreal-UNESCO for Women in Science award and the 5th Edition Science by Women Fellowship through Mujeres por Africa Foundation. Gratitude is extended to the African Academy of Sciences (AAS) for supporting MFT through the affiliates’ program (2019-2023).

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Authors and Affiliations

  1. School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, New Administrative Capital, Egypt

    Nada K. Sedky, Aya L. Allam & Mai F. Tolba

  2. Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt

    Alyaa A. Hamdan & Salma Emad

  3. Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt

    Mohamed Ali

  4. Center of Drug Discovery Research and Development, Ain Shams University, Cairo, Egypt

    Mohamed Ali & Mai F. Tolba

  5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt

    Mai F. Tolba

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  1. Nada K. Sedky
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MFT contributed the work idea and the article structure; NKS drafting the manuscript and combining the different sections and table; MFT and NKS supervision of the work; AAH, SE, AA, MA drafting parts of the manuscript and helped in the table; MA contributed the abstract and figure design; MA and MFT contributed the conclusion section. NKS, MA and MFT revised and finalized the manuscript.

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Correspondence to Mai F. Tolba.

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Sedky, N.K., Hamdan, A.A., Emad, S. et al. Insights into the therapeutic potential of histone deacetylase inhibitor/immunotherapy combination regimens in solid tumors. Clin Transl Oncol 24, 1262–1273 (2022). https://doi.org/10.1007/s12094-022-02779-x

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