Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Häufige urologisch-sexualmedizinische Themen in der Praxis sind das Thema des MMW-Webinars am 5. Juni von 17.30 bis 19 Uhr. Konkret geht es um die Frage, wann bei Harnwegsinfektionen auf Antibiotika verzichtet werden kann, und um ein Update zur Therapie von Libido- und Potenzstörungen des Mannes. Der dritte Vortrag behandelt sexuell übertragbare Krankheiten. Stellen Sie Ihre Fragen an die Experten und sammeln Sie 2 CME-Punkte. Jetzt gleich anmelden!
Erweiterte Suche
Anmelden
nach oben
Clinical and Translational Oncology
Erschienen in: Clinical and Translational Oncology 7/2022

23.01.2022 | Review Article

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

verfasst von: Nada K. Sedky, Alyaa A. Hamdan, Salma Emad, Aya L. Allam, Mohamed Ali, Mai F. Tolba

Erschienen in: Clinical and Translational Oncology | Ausgabe 7/2022

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Cappellacci L, Perinelli DR, Maggi F, et al. Recent progress in histone deacetylase inhibitors as anticancer agents. Curr Med Chem. 2020;27:2449–93.PubMedCrossRef
2.
Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. J Nat Rev Cancer. 2006;6:38–51.CrossRef
3.
Suraweera A, O’Byrne KJ, Richard DJ. Combination therapy with histone deacetylase inhibitors (HDACi) for the treatment of cancer: achieving the full therapeutic potential of HDACi. Front Oncol. 2018;8:92.PubMedPubMedCentralCrossRef
4.
Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5:769–84.PubMedCrossRef
5.
Krämer OH, Mahboobi S, Sellmer A. Drugging the HDAC6–HSP90 interplay in malignant cells. Trends Pharmacol Sci. 2014;35:501–9.PubMedCrossRef
6.
Lin HY, Chen CS, Lin SP, et al. Targeting histone deacetylase in cancer therapy. Med Res Rev. 2006;26:397–413.PubMedCrossRef
7.
Li Y, Shin D, Kwon SH. Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes. FEBS J. 2013;280:775–93.PubMed
8.
9.
Condorelli F, Gnemmi I, Vallario A, et al. Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells. Br J Pharmacol. 2008;153:657–68.PubMedCrossRef
10.
Borbone E, Berlingieri M, De Bellis F, et al. Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation. Oncogene. 2010;29:105–16.PubMedCrossRef
11.
Garmpi A, Garmpis N, Damaskos C, et al. Histone deacetylase inhibitors as a new anticancer option: How far can we go with expectations? Delivery systems. J BUON. 2018;23:846–61.PubMed
12.
Ellis L, Hammers H, Pili R. Targeting tumor angiogenesis with histone deacetylase inhibitors. Cancer Lett. 2009;280:145–53.PubMedCrossRef
13.
El-Naggar AM, Somasekharan SP, Wang Y, et al. Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis. EMBO Rep. 2019;20:e48375.PubMedPubMedCentralCrossRef
14.
Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol. 2016;11:47–76.PubMedCrossRef
15.
Kumar B, Yadav A, Lang JC, et al. Suberoylanilide hydroxamic acid (SAHA) reverses chemoresistance in head and neck cancer cells by targeting cancer stem cells via the downregulation of nanog. Genes cancer. 2015;6:169.PubMedPubMedCentralCrossRef
16.
Jacobs JF, Punt CJ, Lesterhuis WJ, et al. Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients. Clin Cancer Res. 2010;16:5067–78.PubMedCrossRef
17.
Arnould L, Gelly M, Penault-Llorca F, et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer. 2006;94:259–67.PubMedPubMedCentralCrossRef
18.
Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010;363:1324–34.PubMedPubMedCentralCrossRef
19.
Brahmer JR, Pardoll DM. Immune checkpoint inhibitors: making immunotherapy a reality for the treatment of lung cancer. Cancer Immunol Res. 2013;1:85–91.PubMedPubMedCentralCrossRef
20.
21.
Huang W, Chen J-J, Xing R, Zeng Y-C. Combination therapy: Future directions of immunotherapy in small cell lung cancer. Transl Oncol. 2021;14:100889.PubMedCrossRef
22.
Iglesias P. Cancer immunotherapy-induced endocrinopathies: clinical behavior and therapeutic approach. Eur J Intern Med. 2018;47:6–13.PubMedCrossRef
23.
Kroesen M, Lindau D, Hoogerbrugge P, Adema G. Immunocombination therapy for high-risk neuroblastoma. Immunotherapy. 2012;4:163–74.PubMedCrossRef
24.
25.
Bode KA, Schroder K, Hume DA, et al. Histone deacetylase inhibitors decrease Toll-like receptor-mediated activation of proinflammatory gene expression by impairing transcription factor recruitment. Immunology. 2007;122:596–606.PubMedPubMedCentralCrossRef
26.
Deng S, Hu Q, Zhang H, et al. HDAC3 inhibition upregulates PD-L1 expression in B-cell lymphomas and augments the efficacy of anti–PD-L1 therapy. Mol Cancer Ther. 2019;18:900–8.PubMedCrossRef
27.
Tiper IV, Webb TJ. Histone deacetylase inhibitors enhance CD1d-dependent NKT cell responses to lymphoma. Cancer Immunol Immunother. 2016;65:1411–21.PubMedPubMedCentralCrossRef
28.
Bridle BW, Chen L, Lemay CG, et al. HDAC inhibition suppresses primary immune responses, enhances secondary immune responses, and abrogates autoimmunity during tumor immunotherapy. Mol Ther. 2013;21:887–94.PubMedPubMedCentralCrossRef
29.
Sznol M, Kluger HM, Callahan MK, et al. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). American Society of Clinical Oncology; 2014.
30.
31.
Kwiatkowska D, Kluska P, Reich A. Beyond PD-1 immunotherapy in malignant melanoma. Dermatol Ther. 2019;9:243–57.CrossRef
32.
Bretz AC, Parnitzke U, Kronthaler K, et al. Domatinostat favors the immunotherapy response by modulating the tumor immune microenvironment (TIME). J Immunother Cancer. 2019;7:1–15.CrossRef
33.
Bissonnette RP, Cesario RM, Goodenow B, et al. The epigenetic immunomodulator, HBI-8000, enhances the response and reverses resistance to checkpoint inhibitors. BMC Cancer. 2021;21:1–17.CrossRef
34.
Jespersen H, Bagge RO, Ullenhag G, et al. Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): Protocol for a multicenter phase II open label study. BMC Cancer. 2019;19:1–7.CrossRef
35.
Jespersen H, Bagge RO, Ullenhag G, et al. Phase II multicenter open label study of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study). Ann Oncol. 2019;30:v907.CrossRef
36.
Agarwala SS, Moschos SJ, Johnson ML, et al. Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with melanoma progressing on or after a PD-1/L1 blocking antibody. American Society of Clinical Oncology; 2018.CrossRef
37.
Hassel JC, Berking C, Schlaak M, et al. Results from the phase Ib of the SENSITIZE trial combining domatinostat with pembrolizumab in advanced melanoma patients refractory to prior checkpoint inhibitor therapy. Wolters Kluwer Health; 2021.CrossRef
38.
Khushalani N, Brohl A, Markowitz J et al. Significant anti-tumor activity of HBI-8000, a class I histone deacetylase inhibitor (HDACi) in combination with nivolumab (NIVO) in anti-PD1 therapy-naïve advanced melanoma (TN-Mel). J Immunother Cancer. 2020;8(Suppl 3):A476.
39.
Patra SK, Patra A, Dahiya R. Histone deacetylase and DNA methyltransferase in human prostate cancer. Biochem Biophys Res Commun. 2001;287:705–13.PubMedCrossRef
40.
Fu M, Rao M, Wang C, et al. Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. MolCell Biol. 2003;23:8563–75.
41.
Abbas A, Gupta S. The role of histone deacetylases in prostate cancer. Epigenetics. 2008;3:300–9.PubMedCrossRef
42.
Walton T, Li G, Seth R, et al. DNA demethylation and histone deacetylation inhibition co-operate to re-express estrogen receptor beta and induce apoptosis in prostate cancer cell-lines. Prostate. 2008;68:210–22.PubMedCrossRef
43.
Butler LM, Agus DB, Scher HI, et al. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Can Res. 2000;60:5165–70.
44.
Marrocco DL, Tilley WD, Bianco-Miotto T, et al. Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation. Mol Cancer Ther. 2007;6:51–60.PubMedCrossRef
45.
Gameiro SR, Malamas AS, Tsang KY, et al. Inhibitors of histone deacetylase 1 reverse the immune evasion phenotype to enhance T-cell mediated lysis of prostate and breast carcinoma cells. Oncotarget. 2016;7:7390–402.PubMedPubMedCentralCrossRef
46.
Pili R, Quinn DI, Albany C, et al. Immunomodulation by HDAC inhibition: results from a phase Ib study with vorinostat and pembrolizumab in metastatic urothelial, renal, and prostate carcinoma patients. American Society of Clinical Oncology; 2019.
47.
Klein SL, Flanagan KLJNRI. Sex differences in immune responses. Nat Rev Immunol. 2016;16:626.PubMedCrossRef
48.
Ben-Batalla I, Vargas-Delgado ME, Von Amsberg G, et al. Influence of androgens on immunity to self and foreign: effects on immunity and cancer. Front Immunol. 2020;11:1184.PubMedPubMedCentralCrossRef
49.
Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.PubMedCrossRef
50.
Shen L, Pili R. Class I histone deacetylase inhibition is a novel mechanism to target regulatory T cells in immunotherapy. Oncoimmunology. 2012;1:948–50.PubMedPubMedCentralCrossRef
51.
Lin J, Elkon JM, Ricart B, et al. Phase I study of entinostat in combination with enzalutamide for treatment of patients with castration-resistant prostate cancer. American Society of Clinical Oncology; 2021.
52.
Hamam R, Ali AM, Alsaleh KA, et al. microRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection. Sci Rep. 2016;6:1–8.CrossRef
53.
O’Connor O. Clinical experience with the novel histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in patients with relapsed lymphoma. Br J Cancer. 2006;95:S7–12.PubMedCentralCrossRef
54.
Richon V, Webb Y, Merger R, et al. Second generation hybrid polar compounds are potent inducers of transformed cell differentiation. Proc Natl Acad Sci. 1996;93:5705–8.PubMedPubMedCentralCrossRef
55.
Huang L, Pardee ABJMM. Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment. Mol Med. 2000;6:849–66.PubMedPubMedCentralCrossRef
56.
Munster PN, Troso-Sandoval T, Rosen N, et al. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Can Res. 2001;61:8492–7.
57.
58.
Nolan E, Savas P, Policheni AN et al. Combined immune checkpoint blockade as a therapeutic strategy for BRCA1-mutated breast cancer. Sci Transl Med. 2017;9(393):eaal4922. PubMedPubMedCentralCrossRef
59.
Clinicaltrials.gov. Entinostat, nivolumab, and ipilimumab in treating patients with solid tumors that are metastatic or cannot be removed by surgery or locally advanced or metastatic HER2-negative breast cancer. In: 2015; last accessed January 2022.
60.
Basile D, Pelizzari G, Vitale MG, et al. Atezolizumab for the treatment of breast cancer. Expert Opin Biol Ther. 2018;18:595–603.PubMedCrossRef
61.
Varella L, Abraham J, Kruse M. Revisiting the role of bevacizumab in the treatment of breast cancer. Semin Oncol. 2017;44(4):273–285. PubMedCrossRef
62.
Geindreau M, Ghiringhelli F, Bruchard M. Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response. Int J Mol Sci. 2021;22(9):4871.PubMedPubMedCentralCrossRef
63.
Arvind K, Mayur P, Vaibhav R, Arun MK. Impact of ado-trastuzumab emtansine therapy in human epidermal growth factor receptor 2 positive metastatic breast cancer: a recent survey. Asian J Pharm. 2016;10:S444.
64.
65.
Shen L, Ciesielski M, Ramakrishnan S, et al. Class I histone deacetylase inhibitor entinostat suppresses regulatory T cells and enhances immunotherapies in renal and prostate cancer models. PLoS ONE. 2012;7:e30815.PubMedPubMedCentralCrossRef
66.
Kato Y, Yoshimura K, Shin T, et al. Synergistic in vivo antitumor effect of the histone deacetylase inhibitor MS-275 in combination with interleukin 2 in a murine model of renal cell carcinoma. Clin Cancer Res. 2007;13:4538–46.PubMedCrossRef
67.
68.
Beier UH, Akimova T, Liu Y, et al. Histone/protein deacetylases control Foxp3 expression and the heat shock response of T-regulatory cells. Curr Opin Immunol. 2011;23:670–8.PubMedPubMedCentralCrossRef
69.
Wang L, Beier U, Akimova T, et al. Histone/protein deacetylase inhibitor therapy for enhancement of Foxp3+ T-regulatory cell function posttransplantation. Am J Transplant. 2018;18:1596–603.PubMedPubMedCentralCrossRef
70.
Coral S, Sigalotti L, Colizzi F, et al. Phenotypic and functional changes of human melanoma xenografts induced by DNA hypomethylation: immunotherapeutic implications. J Cell Physiol. 2006;207:58–66.PubMedCrossRef
71.
Adair SJ, Hogan KT. Treatment of ovarian cancer cell lines with 5-aza-2′-deoxycytidine upregulates the expression of cancer-testis antigens and class I major histocompatibility complex-encoded molecules. Cancer Immunol Immunother. 2009;58:589–601.PubMedCrossRef
72.
Bao L, Dunham K, Lucas K. MAGE-A1, MAGE-A3, and NY-ESO-1 can be upregulated on neuroblastoma cells to facilitate cytotoxic T lymphocyte-mediated tumor cell killing. Cancer Immunol Immunother. 2011;60:1299.PubMedCrossRef
73.
Krishnadas DK, Bao L, Bai F, et al. Decitabine facilitates immune recognition of sarcoma cells by upregulating CT antigens, MHC molecules, and ICAM-1. Tumor Biology. 2014;35:5753–62.PubMedCrossRef
74.
Azad NS, Shirai K, Mcree AJ, et al. ENCORE 601: a phase 2 study of entinostat in combination with pembrolizumab in patients with microsatellite stable metastatic colorectal cancer. J Clin Oncol. 2018;36:3557.CrossRef
75.
Murphy AG, Walker R, Lutz ER, et al. Epigenetic priming prior to pembrolizumab in mismatch repair-proficient advanced colorectal cancer. American Society of Clinical Oncology; 2019.CrossRef
76.
Andre T, Lonardi S, Wong M et al. Nivolumab+ ipilimumab combination in patients with DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer: first report of the full cohort from CheckMate-142. J Clin Oncol. 2018;36(4):553–553.CrossRef
77.
Saunders MP, Graham J, Cunningham D, et al. A phase Ib/II trial to assess the safety and efficacy of CXD101 in combination with the PD-1 inhibitor nivolumab in patients with metastatic, previously-treated, microsatellite-stable (MSS) colorectal carcinoma (short title CAROSELL). Ann Oncol. 2019;30:v250.CrossRef
78.
Connolly RM, Li H, Jankowitz RC, et al. Combination epigenetic therapy in advanced breast cancer with 5-azacitidine and entinostat: a phase II National Cancer Institute/Stand Up to Cancer Study. Clin Cancer Res. 2017;23:2691–701.PubMedCrossRef
79.
Weintraub K. Take two: combining immunotherapy with epigehetic drugs to tackle cancer. Nat Med. 2016;22:8–11.PubMedCrossRef
80.
Beg AA, Gray JE. HDAC inhibitors with PD-1 blockade: a promising strategy for treatment of multiple cancer types? Epigenomics. 2016;8:1015–7.PubMedCrossRef
81.
82.
Hashimoto A, Fukumoto T, Zhang R, Gabrilovich D. Selective targeting of different populations of myeloid-derived suppressor cells by histone deacetylase inhibitors. Cancer Immunol Immunother. 2020;69:1929–36.PubMedPubMedCentralCrossRef
83.
Gray JE, Saltos A, Tanvetyanon T, et al. Phase I/Ib study of pembrolizumab plus vorinostat in advanced/metastatic Non–small cell lung cancer. Clin Cancer Res. 2019;25:6623–32.PubMedPubMedCentralCrossRef
84.
Terranova-Barberio M, Thomas S, Ali N, et al. HDAC inhibition potentiates immunotherapy in triple negative breast cancer. Oncotarget. 2017;8:114156.PubMedPubMedCentralCrossRef
85.
Barberio MT, Thomas S, Ali N, et al. Abstract B10: HDAC inhibition modulates immune checkpoint pathway in triple-negative breast cancer. American Association for Cancer Research; 2018.
Metadaten
Titel
Insights into the therapeutic potential of histone deacetylase inhibitor/immunotherapy combination regimens in solid tumors
verfasst von
Nada K. Sedky
Alyaa A. Hamdan
Salma Emad
Aya L. Allam
Mohamed Ali
Mai F. Tolba
Publikationsdatum
23.01.2022
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 7/2022
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-022-02779-x

Weitere Artikel der Ausgabe 7/2022

Clinical and Translational Oncology 7/2022 Zur Ausgabe

Research Article

A novel immune-related RNA-binding proteins signature to predict survival and therapeutic responses in prostate cancer

Correction

Correction to: SEOM‑GEMCAD‑TTD clinical guidelines for localized rectal cancer (2021)

Special Article

Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer

Research Article

RNA modification “writer”-mediated RNA modification patterns and tumor microenvironment characteristics of cervical cancer

Review Article

Platelets for cancer treatment and drug delivery

Review Article

The role of EphA7 in different tumors

Neu im Fachgebiet Onkologie

Hodgkin Lymphom: BrECADD-Regime übertrifft die Erwartungen

05.06.2024 ASCO 2024 Kongressbericht

Das Kombinationsregime BrECADD mit Brentuximab vedotin ermöglichte in der Studie HD21 beim fortgeschrittenen klassischen Hodgkin-Lymphom eine unerwartet hohe progressionsfreie Überlebensrate von 94,3% nach vier Jahren. Gleichzeitig war das Regime besser tolerabel als der bisherige Standard eBEACOPP.

Brustkrebs-Prävention wird neu gedacht

04.06.2024 ASCO 2024 Kongressbericht

Zurzeit untersuchen Forschende verschiedene neue Ansätze zur Prävention von Brustkrebs bei Personen mit hohem Risiko. Darunter Denosumab, die prophylaktische Bestrahlung der Brust – und Impfungen.

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

04.06.2024 Levonorgestrel Nachrichten

Unter Frauen, die ein Levonorgestrel-freisetzendes intrauterines System (IUS) verwenden, ist die Brustkrebsrate um 13% erhöht. Dafür kommt es deutlich seltener zu Endometrium-, Zervix- und Ovarialkarzinomen.

Beim Melanom könnte „Operation zuerst“ zum Auslaufmodell werden

03.06.2024 ASCO 2024 Kongressbericht

Nicht nur besser, auch viel kürzer: Die neoadjuvante Melanom-Therapie mit Checkpoint-Inhibitoren beeindruckt in der Erstauswertung der NADINA-Studie. Sie könnte ein neuer Standard werden.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise