Hostname: page-component-5d59c44645-lfgmx Total loading time: 0 Render date: 2024-02-27T08:31:29.089Z Has data issue: false hasContentIssue false

Efficacy of immune checkpoint inhibitor monotherapy or combined with other small molecule-targeted agents in ovarian cancer

Published online by Cambridge University Press:  24 January 2023

Munawaer Muaibati
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Abasi Abuduyilimu
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Tao Zhang
Affiliation:
Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Yun Dai
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Ruyuan Li
Affiliation:
Department of Gynecology and Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Fanwei Huang
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Kexin Li
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Qing Tong
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Xiaoyuan Huang
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Liang Zhuang*
Affiliation:
Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
*
Author for correspondence: Liang Zhuang, E-mail: mrzhuangliang@126.com

Abstract

Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.

Type
Review
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Siegel, RL et al. (2018) Cancer statistics. CA: A Cancer Journal for Clinicians 68, 730.Google ScholarPubMed
Torre, LA et al. (2018) Ovarian cancer statistics. CA: A Cancer Journal for Clinicians 68, 284296.Google ScholarPubMed
Hennessy, BT et al. (2009) Ovarian cancer. Lancet 374, 13711382.CrossRefGoogle ScholarPubMed
Siegel, RL et al. (2017) Cancer statistics. CA: A Cancer Journal for Clinicians 67, 730.Google ScholarPubMed
Odunsi, K (2017) Immunotherapy in ovarian cancer. Annals of Oncology 28, viii1viii7.CrossRefGoogle ScholarPubMed
Anadon, CM et al. (2022) Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell 40, 545557.e513.CrossRefGoogle ScholarPubMed
Maiorano, BA et al. (2021) Ovarian cancer in the era of immune checkpoint inhibitors: state of the art and future perspectives. Cancers (Basel) 13, 4438.CrossRefGoogle ScholarPubMed
Yin, M et al. (2016) Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. Journal of Clinical Investigation 126, 41574173.CrossRefGoogle ScholarPubMed
Kolomeyevskaya, N et al. (2015) Cytokine profiling of ascites at primary surgery identifies an interaction of tumor necrosis factor-α and interleukin-6 in predicting reduced progression-free survival in epithelial ovarian cancer. Gynecologic Oncology 138, 352357.CrossRefGoogle ScholarPubMed
Yuan, X et al. (2017) Prognostic significance of tumor-associated macrophages in ovarian cancer: a meta-analysis. Gynecologic Oncology 147, 181187.CrossRefGoogle ScholarPubMed
Curiel, TJ et al. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Medicine 10, 942949.CrossRefGoogle ScholarPubMed
Edner, NM et al. (2020) Targeting co-stimulatory molecules in autoimmune disease. Nature Reviews. Drug Discovery 19, 860883.CrossRefGoogle ScholarPubMed
Jiang, X et al. (2019) Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Molecular Cancer 18, 10.CrossRefGoogle ScholarPubMed
Hirano, F et al. (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Research 65, 10891096.CrossRefGoogle ScholarPubMed
Okazaki, T et al. (2001) PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting Src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proceedings of the National Academy of Sciences of the USA 98, 1386613871.CrossRefGoogle ScholarPubMed
Egen, JG et al. (2002) CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nature Immunology 3, 611618.CrossRefGoogle ScholarPubMed
Lingel, H et al. (2019) CTLA-4 (CD152): a versatile receptor for immune-based therapy. Seminars in Immunology 42, 101298.CrossRefGoogle ScholarPubMed
Goldberg, MV et al. (2011) LAG-3 in cancer immunotherapy. Current Topics in Microbiology and Immunology 344, 269278.Google ScholarPubMed
Workman, CJ et al. (2004) Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo. Journal of Immunology 172, 54505455.CrossRefGoogle ScholarPubMed
Workman, CJ et al. (2002) Cutting edge: molecular analysis of the negative regulatory function of lymphocyte activation gene-3. Journal of Immunology 169, 53925395.CrossRefGoogle ScholarPubMed
Chiba, S et al. (2012) Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nature Immunology 13, 832842.CrossRefGoogle ScholarPubMed
Kang, CW et al. (2015) Apoptosis of tumor infiltrating effector TIM-3+CD8+ T cells in colon cancer. Scientific Reports 5, 15659.CrossRefGoogle ScholarPubMed
Murga-Zamalloa, CA et al. (2020) Expression of the checkpoint receptors LAG-3, TIM-3 and VISTA in peripheral T cell lymphomas. Journal of Clinical Pathology 73, 197203.CrossRefGoogle ScholarPubMed
Zhao, L et al. (2021) TIM-3: an update on immunotherapy. International Immunopharmacology 99, 107933.CrossRefGoogle ScholarPubMed
Chauvin, JM et al. (2020) TIGIT in cancer immunotherapy. Journal for Immunotherapy of Cancer 8, e000957.CrossRefGoogle ScholarPubMed
Dougall, WC et al. (2017) TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunological Reviews 276, 112120.CrossRefGoogle ScholarPubMed
Han, P et al. (2004) An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection. Journal of Immunology 172, 59315939.CrossRefGoogle ScholarPubMed
Sedy, JR et al. (2005) B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nature Immunology 6, 9098.CrossRefGoogle Scholar
Hosseinkhani, N et al. (2021) The role of V-domain Ig suppressor of T cell activation (VISTA) in cancer therapy: lessons learned and the road ahead. Frontiers in Immunology 12, 676181.CrossRefGoogle ScholarPubMed
Johnston, RJ et al. (2019) VISTA is an acidic pH-selective ligand for PSGL-1. Nature 574, 565570.CrossRefGoogle ScholarPubMed
Tang, K et al. (2021) Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors in clinical trials for cancer immunotherapy. Journal of Hematology & Oncology 14, 68.CrossRefGoogle ScholarPubMed
Ishida, Y et al. (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO Journal 11, 38873895.CrossRefGoogle ScholarPubMed
Nishimura, H et al. (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11, 141151.CrossRefGoogle ScholarPubMed
Marasco, M et al. (2020) Molecular mechanism of SHP2 activation by PD-1 stimulation. Science Advances 6, eaay4458.CrossRefGoogle ScholarPubMed
Terme, M et al. (2011) IL-18 induces PD-1-dependent immunosuppression in cancer. Cancer Research 71, 53935399.CrossRefGoogle ScholarPubMed
Matsuzaki, J et al. (2010) Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proceedings of the National Academy of Sciences of the USA 107, 78757880.CrossRefGoogle ScholarPubMed
Tu, L et al. (2020) Assessment of the expression of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival. International Journal of Cancer 147, 423439.CrossRefGoogle ScholarPubMed
Rådestad, E et al. (2019) Immune profiling and identification of prognostic immune-related risk factors in human ovarian cancer. Oncoimmunology 8, e1535730.CrossRefGoogle ScholarPubMed
Hensler, M et al. (2020) M2-like macrophages dictate clinically relevant immunosuppression in metastatic ovarian cancer. Journal for Immunotherapy of Cancer 8, e000979.CrossRefGoogle ScholarPubMed
Maine, CJ et al. (2014) Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer. Cancer Immunology Immunotherapy 63, 215224.CrossRefGoogle ScholarPubMed
Abiko, K et al. (2013) PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction. Clinical Cancer Research 19, 13631374.CrossRefGoogle ScholarPubMed
Parvathareddy, SK et al. (2021) Differential expression of PD-L1 between primary and metastatic epithelial ovarian cancer and its clinico-pathological correlation. Scientific Reports 11, 3750.CrossRefGoogle ScholarPubMed
Darb-Esfahani, S et al. (2016) Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma. Oncotarget 7, 14861499.CrossRefGoogle ScholarPubMed
Linsley, PS et al. (1991) CTLA-4 is a second receptor for the B cell activation antigen B7. Journal of Experimental Medicine 174, 561569.CrossRefGoogle ScholarPubMed
Krummel, MF et al. (1995) CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. Journal of Experimental Medicine 182, 459465.CrossRefGoogle ScholarPubMed
Duraiswamy, J et al. (2013) Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Research 73, 35913603.CrossRefGoogle ScholarPubMed
Huard, B et al. (1995) CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins. European Journal of Immunology 25, 27182721.CrossRefGoogle ScholarPubMed
Grosso, JF et al. (2007) LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. Journal of Clinical Investigation 117, 33833392.CrossRefGoogle ScholarPubMed
Kouo, T et al. (2015) Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells. Cancer Immunology Research 3, 412423.CrossRefGoogle ScholarPubMed
Xu, F et al. (2014) LSECTin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses. Cancer Research 74, 34183428.CrossRefGoogle ScholarPubMed
Wang, J et al. (2019) Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell 176, 334347.e312.CrossRefGoogle Scholar
Woo, SR et al. (2012) Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Research 72, 917927.CrossRefGoogle ScholarPubMed
Huang, RY et al. (2015) LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model. Oncotarget 6, 2735927377.CrossRefGoogle Scholar
Das, M et al. (2017) TIM-3 and its role in regulating anti-tumor immunity. Immunological Reviews 276, 97111.CrossRefGoogle ScholarPubMed
Zhu, C et al. (2005) The TIM-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nature Immunology 6, 12451252.CrossRefGoogle ScholarPubMed
Santiago, C et al. (2007) Structures of T cell immunoglobulin mucin protein 4 show a metal-ion-dependent ligand binding site where phosphatidylserine binds. Immunity 27, 941951.CrossRefGoogle ScholarPubMed
Xu, Y et al. (2017) Role of TIM-3 in ovarian cancer. Clinical & Translational Oncology 19, 10791083.CrossRefGoogle ScholarPubMed
Yan, J et al. (2013) TIM-3 expression defines regulatory T cells in human tumors. PLoS ONE 8, e58006.CrossRefGoogle ScholarPubMed
Sakuishi, K et al. (2013) TIM3(+)FOXP3(+) regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer. Oncoimmunology 2, e23849.CrossRefGoogle ScholarPubMed
Whelan, S et al. (2019) PVRIG and PVRL2 are induced in cancer and inhibit CD8(+) T-cell function. Cancer Immunology Research 7, 257268.CrossRefGoogle ScholarPubMed
Li, YC et al. (2020) Overexpression of an immune checkpoint (CD155) in breast cancer associated with prognostic significance and exhausted tumor-infiltrating lymphocytes: a cohort study. Journal of Immunology Research 2020, 3948928.CrossRefGoogle ScholarPubMed
Harjunpää, H et al. (2020) TIGIT as an emerging immune checkpoint. Clinical and Experimental Immunology 200, 108119.CrossRefGoogle ScholarPubMed
Maas, RJ et al. (2020) TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1/TIGIT/CD96 checkpoint molecules in ovarian cancer. Oncoimmunology 9, 1843247.CrossRefGoogle ScholarPubMed
Chen, F et al. (2020) TIGIT enhances CD4(+) regulatory T-cell response and mediates immune suppression in a murine ovarian cancer model. Cancer Medicine 9, 35843591.CrossRefGoogle Scholar
Yu, X et al. (2019) BTLA/HVEM signaling: milestones in research and role in chronic hepatitis B virus infection. Frontiers in Immunology 10, 617.CrossRefGoogle ScholarPubMed
Zhang, T et al. (2016) Knockdown of HVEM, a lymphocyte regulator gene, in ovarian cancer cells increases sensitivity to activated T cells. Oncology Research 24, 189196.CrossRefGoogle ScholarPubMed
Chen, YL et al. (2019) BTLA blockade enhances cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes. Journal for Immunotherapy of Cancer 7, 313.CrossRefGoogle ScholarPubMed
Lines, JL et al. (2014) VISTA is an immune checkpoint molecule for human T cells. Cancer Research 74, 19241932.CrossRefGoogle ScholarPubMed
ElTanbouly, MA et al. (2020) VISTA: coming of age as a multi-lineage immune checkpoint. Clinical and Experimental Immunology 200, 120130.CrossRefGoogle ScholarPubMed
Mulati, K et al. (2019) VISTA expressed in tumour cells regulates T cell function. British Journal of Cancer 120, 115127.CrossRefGoogle ScholarPubMed
Zong, L et al. (2020) VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer. Cancer Immunology Immunotherapy 69, 3342.CrossRefGoogle ScholarPubMed
Liu, M et al. (2018) Targeting the IDO1 pathway in cancer: from bench to bedside. Journal of Hematology & Oncology 11, 100.CrossRefGoogle ScholarPubMed
Wainwright, DA et al. (2012) IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clinical Cancer Research 18, 61106121.CrossRefGoogle ScholarPubMed
Mellor, AL et al. (2002) Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses. Journal of Immunology 168, 37713776.CrossRefGoogle ScholarPubMed
Qian, F et al. (2009) Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2,3-dioxygenase-mediated arrest of T-cell proliferation in human epithelial ovarian cancer. Cancer Research 69, 54985504.CrossRefGoogle ScholarPubMed
Okamoto, A et al. (2005) Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clinical Cancer Research 11, 60306039.CrossRefGoogle ScholarPubMed
Takao, M et al. (2007) Increased synthesis of indoleamine-2,3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer. Oncology Reports 17, 13331339.Google Scholar
Amobi-McCloud, A et al. (2021) IDO1 expression in ovarian cancer induces PD-1 in T cells via aryl hydrocarbon receptor activation. Frontiers in Immunology 12, 678999.CrossRefGoogle Scholar
Boland, JL et al. (2019) Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade. Gynecologic Oncology 152, 251258.CrossRefGoogle ScholarPubMed
Wolchok, JD et al. (2010) Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. The Lancet. Oncology 11, 155164.CrossRefGoogle ScholarPubMed
Hodi, FS et al. (2010) Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine 363, 711723.CrossRefGoogle ScholarPubMed
Zamarin, D et al. (2020) Randomized phase II trial of nivolumab versus nivolumab and ipilimumab for recurrent or persistent ovarian cancer: an NRG oncology study. Journal of Clinical Oncology 38, 18141823.CrossRefGoogle ScholarPubMed
Hamanishi, J et al. (2015) Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. Journal of Clinical Oncology 33, 40154022.CrossRefGoogle ScholarPubMed
Hamanishi, J et al. (2021) Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant ovarian cancer: open-label, randomized trial in Japan (NINJA). Journal of Clinical Oncology 39, 36713681.CrossRefGoogle ScholarPubMed
Matulonis, UA et al. (2019) Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Annals of Oncology 30, 10801087.CrossRefGoogle ScholarPubMed
Walsh, CS et al. (2021) Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. PLoS ONE 16, e0252665.CrossRefGoogle ScholarPubMed
Lee, EK et al. (2020) Combined pembrolizumab and pegylated liposomal doxorubicin in platinum resistant ovarian cancer: a phase 2 clinical trial. Gynecologic Oncology 159, 7278.CrossRefGoogle ScholarPubMed
Varga, A et al. (2019) Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: analysis of KEYNOTE-028. Gynecologic Oncology 152, 243250.CrossRefGoogle ScholarPubMed
Nishio, S et al. (2020) Pembrolizumab monotherapy in Japanese patients with advanced ovarian cancer: subgroup analysis from the KEYNOTE-100. Cancer Science 111, 13241332.CrossRefGoogle ScholarPubMed
Rahma, OE et al. (2022) Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. Journal for Immunotherapy of Cancer 10, e003569.CrossRefGoogle ScholarPubMed
Brahmer, JR et al. (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New England Journal of Medicine 366, 24552465.CrossRefGoogle ScholarPubMed
Taylor, K et al. (2020) An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors. Journal for Immunotherapy of Cancer 8, e000883.CrossRefGoogle ScholarPubMed
Ngoi, NY et al. (2020) A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician's choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA). International Journal of Gynecological Cancer 30, 12391242.CrossRefGoogle ScholarPubMed
Lee, JY et al. (2019) A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean gynecologic oncology group study (KGOG 3046), TRU-D. Journal of Gynecologic Oncology 30, e112.CrossRefGoogle Scholar
Liu, JF et al. (2019) Safety, clinical activity and biomarker assessments of atezolizumab from a phase I study in advanced/recurrent ovarian and uterine cancers. Gynecologic Oncology 154, 314322.CrossRefGoogle ScholarPubMed
Pujade-Lauraine, E et al. (2021) Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN ovarian 200): an open-label, three-arm, randomised, phase 3 study. The Lancet. Oncology 22, 10341046.CrossRefGoogle ScholarPubMed
Pujade-Lauraine, E et al. (2018) Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN ovarian 200 phase III study design. Future Oncology 14, 21032113.CrossRefGoogle ScholarPubMed
Monk, BJ et al. (2021) Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN ovarian 100): an open-label, randomised, phase 3 trial. The Lancet. Oncology 22, 12751289.CrossRefGoogle ScholarPubMed
Disis, ML et al. (2019) Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial. JAMA Oncology 5, 393401.CrossRefGoogle ScholarPubMed
Ansell, SM et al. (2009) Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clinical Cancer Research 15, 64466453.CrossRefGoogle ScholarPubMed
Normann, MC et al. (2019) Early experiences with PD-1 inhibitor treatment of platinum resistant epithelial ovarian cancer. Journal of Gynecologic Oncology 30, e56.CrossRefGoogle ScholarPubMed
Linette, GP et al. (2019) Tumor-infiltrating lymphocytes in the checkpoint inhibitor era. Current Hematologic Malignancy Reports 14, 286291.CrossRefGoogle ScholarPubMed
Cheng, WC et al. (2019) Firing up cold tumors. Trends in Cancer 5, 528530.CrossRefGoogle ScholarPubMed
Bezu, L et al. (2015) Combinatorial strategies for the induction of immunogenic cell death. Frontiers in Immunology 6, 187.Google ScholarPubMed
Lheureux, S et al. (2020) EVOLVE: a multicenter open-label single-arm clinical and translational phase II trial of cediranib plus olaparib for ovarian cancer after PARP inhibition progression. Clinical Cancer Research 26, 42064215.CrossRefGoogle ScholarPubMed
Liu, JF et al. (2019) Assessment of combined nivolumab and bevacizumab in relapsed ovarian cancer: a phase 2 clinical trial. JAMA Oncology 5, 17311738.CrossRefGoogle ScholarPubMed
Zsiros, E et al. (2021) Efficacy and safety of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of recurrent ovarian cancer: a phase 2 nonrandomized clinical trial. JAMA Oncology 7, 7885.CrossRefGoogle ScholarPubMed
Moore, KN et al. (2021) Atezolizumab, bevacizumab, and chemotherapy for newly diagnosed stage III or IV ovarian cancer: placebo-controlled randomized phase III trial (IMagyn050/GOG 3015/ENGOT-OV39). Journal of Clinical Oncology 39, 18421855.CrossRefGoogle ScholarPubMed
Moroney, JW et al. (2020) Safety and clinical activity of atezolizumab plus bevacizumab in patients with ovarian cancer: a phase Ib study. Clinical Cancer Research 26, 56315637.CrossRefGoogle ScholarPubMed
Gonzalez Martin, A et al. (2021) A phase III, randomized, double blinded trial of platinum based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal, or peritoneal cancer and platinum treatment free interval of more than 6 months: ENGOT-Ov41/GEICO 69-O/ANITA trial. International Journal of Gynecological Cancer 31, 617622.CrossRefGoogle ScholarPubMed
Lee, YJ et al. (2021) A single-arm phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer (OPEB-01). Journal of Gynecologic Oncology 32, e31.CrossRefGoogle ScholarPubMed
Lampert, EJ et al. (2020) Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase II study. Clinical Cancer Research 26, 42684279.CrossRefGoogle ScholarPubMed
Fumet, JD et al. (2020) Precision medicine phase II study evaluating the efficacy of a double immunotherapy by durvalumab and tremelimumab combined with olaparib in patients with solid cancers and carriers of homologous recombination repair genes mutation in response or stable after olaparib treatment. BMC Cancer 20, 748.CrossRefGoogle ScholarPubMed
Zimmer, AS et al. (2019) A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses. Journal for Immunotherapy of Cancer 7, 197.CrossRefGoogle Scholar
Lee, JY et al. (2022) Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial. Journal of Gynecologic Oncology 33, e45.CrossRefGoogle ScholarPubMed
Monk, BJ et al. (2021) ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer. International Journal of Gynecological Cancer 31, 15891594.CrossRefGoogle ScholarPubMed
Jung, KH et al. (2019) Phase I study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) administered with PD-L1 inhibitor (atezolizumab) in advanced solid tumors. Clinical Cancer Research 25, 32203228.CrossRefGoogle Scholar
Chen, S et al. (2022) Epigenetic priming enhances antitumor immunity in platinum-resistant ovarian cancer. Journal of Clinical Investigation 132, e158800.CrossRefGoogle ScholarPubMed
Zamarin, D et al. (2020) Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. Journal for Immunotherapy of Cancer 8, e000829.CrossRefGoogle ScholarPubMed
Falchook, GS et al. (2021) A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. Investigational New Drugs 39, 12841297.CrossRefGoogle ScholarPubMed
Rocconi, RP et al. (2022) Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer. Cancer Gene Therapy 29, 369382.CrossRefGoogle ScholarPubMed
Simonelli, M et al. (2022) Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study. ESMO Open 7, 100562.CrossRefGoogle ScholarPubMed
Li, J et al. (2019) Expanding the role of STING in cellular homeostasis and transformation. Trends in Cancer 5, 195197.CrossRefGoogle ScholarPubMed
Curdy, N et al. (2019) Regulatory mechanisms of inhibitory immune checkpoint receptors expression. Trends in Cell Biology 29, 777790.CrossRefGoogle ScholarPubMed
Huang, RY et al. (2017) Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer. Oncoimmunology 6, e1249561.CrossRefGoogle ScholarPubMed
Venkitaraman, AR (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108, 171182.CrossRefGoogle ScholarPubMed
Konstantinopoulos, PA et al. (2015) Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discovery 5, 11371154.CrossRefGoogle ScholarPubMed
Pilié, PG et al. (2019) State-of-the-art strategies for targeting the DNA damage response in cancer. Nature Reviews. Clinical Oncology 16, 81104.CrossRefGoogle ScholarPubMed
Foo, T et al. (2021) PARP inhibitors in ovarian cancer: an overview of the practice-changing trials. Genes Chromosomes & Cancer 60, 385397.CrossRefGoogle ScholarPubMed
Zheng, F et al. (2020) Mechanism and current progress of poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomedicine & Pharmacotherapy 123, 109661.CrossRefGoogle ScholarPubMed
da Cunha Colombo Bonadio, RR et al. (2018) Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics (Sao Paulo) 73, e450s.CrossRefGoogle ScholarPubMed
Ding, L et al. (2018) PARP inhibition elicits STING-dependent antitumor immunity in BRCA1-deficient ovarian cancer. Cell Reports 25, 29722980.e2975.CrossRefGoogle ScholarPubMed
Wang, Z et al. (2019) Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models. Scientific Reports 9, 1853.CrossRefGoogle ScholarPubMed
Shen, J et al. (2019) PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness. Cancer Research 79, 311319.CrossRefGoogle ScholarPubMed
Konstantinopoulos, PA et al. (2019) Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncology 5, 11411149.CrossRefGoogle ScholarPubMed
Bekes, I et al. (2016) Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer? Molecular Cancer 15, 13.CrossRefGoogle ScholarPubMed
Nagy, JA et al. (1995) Pathogenesis of ascites tumor growth: vascular permeability factor, vascular hyperpermeability, and ascites fluid accumulation. Cancer Research 55, 360368.Google ScholarPubMed
Luo, JC et al. (1998) Significant expression of vascular endothelial growth factor/vascular permeability factor in mouse ascites tumors. Cancer Research 58, 26522660.Google ScholarPubMed
Mahner, S et al. (2010) TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients. BMC Cancer 10, 139.CrossRefGoogle ScholarPubMed
Azam, F et al. (2010) Mechanisms of resistance to antiangiogenesis therapy. European Journal of Cancer 46, 13231332.CrossRefGoogle ScholarPubMed
Bergers, G et al. (2008) Modes of resistance to anti-angiogenic therapy. Nature Reviews Cancer 8, 592603.CrossRefGoogle ScholarPubMed
Yang, Y et al. (2021) Programmed death ligand-1 regulates angiogenesis and metastasis by participating in the c-JUN/VEGFR2 signaling axis in ovarian cancer. Cancer Communications 41, 511527.CrossRefGoogle ScholarPubMed
Klose, RJ et al. (2006) Genomic DNA methylation: the mark and its mediators. Trends in Biochemical Sciences 31, 8997.CrossRefGoogle ScholarPubMed
Ahluwalia, A et al. (2001) DNA methylation in ovarian cancer. II. Expression of DNA methyltransferases in ovarian cancer cell lines and normal ovarian epithelial cells. Gynecologic Oncology 82, 299304.CrossRefGoogle ScholarPubMed
Stone, TW et al. (2013) An expanding range of targets for kynurenine metabolites of tryptophan. Trends in Pharmacological Sciences 34, 136143.CrossRefGoogle ScholarPubMed
Li, F et al. (2017) IDO1: an important immunotherapy target in cancer treatment. International Immunopharmacology 47, 7077.CrossRefGoogle ScholarPubMed
Choi, SW et al. (2000) Folate and carcinogenesis: an integrated scheme. Journal of Nutrition 130, 129132.CrossRefGoogle ScholarPubMed
Scaranti, M et al. (2020) Exploiting the folate receptor α in oncology. Nature Reviews. Clinical Oncology 17, 349359.CrossRefGoogle ScholarPubMed
Figini, M et al. (2003) Reversion of transformed phenotype in ovarian cancer cells by intracellular expression of anti folate receptor antibodies. Gene Therapy 10, 10181025.CrossRefGoogle ScholarPubMed
Nawaz, FZ et al. (2022) Emerging roles for folate receptor FOLR1 in signaling and cancer. Trends in Endocrinology and Metabolism 33, 159174.CrossRefGoogle ScholarPubMed
Wade, PA et al. (1997) Histone acetylation: chromatin in action. Trends in Biochemical Sciences 22, 128132.CrossRefGoogle ScholarPubMed
Eckschlager, T et al. (2017) Histone deacetylase inhibitors as anticancer drugs. International Journal of Molecular Sciences 18, 1414.CrossRefGoogle ScholarPubMed
Li, Y et al. (2016) HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harbor Perspectives in Medicine 6, a026831.CrossRefGoogle ScholarPubMed
Weichert, W et al. (2008) Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas. Neoplasia (New York, N.Y.) 10, 10211027.CrossRefGoogle ScholarPubMed
Yano, M et al. (2018) Association of histone deacetylase expression with histology and prognosis of ovarian cancer. Oncology Letters 15, 35243531.Google ScholarPubMed
Roberts, PJ et al. (2007) Targeting the Raf–MEK–ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26, 32913310.CrossRefGoogle ScholarPubMed
De Luca, A et al. (2012) The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opinion on Therapeutic Targets 16(suppl. 2), S17S27.CrossRefGoogle ScholarPubMed
Shrestha, R et al. (2021) Multiomics characterization of low-grade serous ovarian carcinoma identifies potential biomarkers of MEK inhibitor sensitivity and therapeutic vulnerability. Cancer Research 81, 16811694.CrossRefGoogle ScholarPubMed