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. 2019 Aug;29(Suppl 2):s16-s21.
doi: 10.1136/ijgc-2019-000456.

Novel therapeutics: response and resistance in ovarian cancer

Dmitriy Zamarin  1
Affiliations

Novel therapeutics: response and resistance in ovarian cancer

Dmitriy Zamarin. Int J Gynecol Cancer. 2019 Aug.

Abstract

Here we review the latest pre-clinical and clinical developments for treatment of ovarian cancer, presented at the American Association of Cancer Research/Rivkin Center Ovarian Cancer Research Symposium held at the University of Washington in September 2018. Abstracts and presentations pertaining to the 'Novel Therapeutics' session were reviewed and are summarized here. The session featured a keynote presentation from Dr Ursula Matulonis, who summarized the current state of the art of treatment of ovarian cancer, including recent clinical trials incorporating the use of novel agents, including poly-ADP-ribose polymerase (PARP) inhibitors, other DNA-damaging agents, vascular endothelial growth factor receptor inhibitors, mirvetuximab soravtansine, and immune checkpoint blockade. Dr Jung-Min Lee then summarized the rationale and the results of early studies for targeting cell cycle checkpoint kinases for anti-cancer therapy. Eight submissions were selected for oral presentations, and 36 abstracts were presented as posters. The topics covered a range of clinical and pre-clinical strategies and biomarkers, including immunotherapy, mechanisms of chemotherapy, and PARP inhibitor resistance, DNA-damaging agents, and other novel therapeutic strategies. Key studies have highlighted that resistance to chemotherapy and PARP inhibitors remain a major challenge in therapy of ovarian cancer. Cancer stem cells represent an important mechanism of chemoresistance and strategies to target these cells may be a pathway to prevention of ovarian cancer relapse. Advancement of novel therapeutics targeting DNA damage, cell metabolism, and endoplasmic reticulum present some of the novel strategies in the pipeline. Emerging compelling pre-clinical data with novel antibody-drug conjugates targeting various surface receptors in ovarian cancer alone and in combination with immune checkpoint blockade generate a strong enthusiasm for rapid translation of these strategies to clinic.

Keywords: ovarian cancer.

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Conflict of interest statement

Competing interests: DZ indicated financial activities outside of the submitted work, which include personal fees, grants, and intellectual property.

References

    1. Konstantinopoulos P, Munster P, Forero-Torres A, Holloway R, Schwartzberg L, Matulonis U, Wang J, Guo W, Dezube B, and Vinayak S, TOPACIO: preliminary activity and safety in patients (pts) with platinum-resistant ovarian cancer in a phase 1/2 study of niraparib in combination with pembrolizumab, in SGO Annual Meeting; March 24-27. 2018: New Orleans, LA.
    1. Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, and Matulonis UA, Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol, 2014. 15(11): p. 1207–14.PMC4294183,http://www.ncbi.nlm.nih.gov/pubmed/25218906 - PMC - PubMed
    1. Konstantinopoulos PA, Barry W, Birrer M, Westin SN, Farooq S, C. K, Whalen C, Luo W, Liu H, Aghajanian C, Solit DB, Mills GB, Taylor B, Won H, Berger M, Palakurthi S, Liu JF, Cantley L, Kaufmann SH, Swisher EM, D’Andrea AD, Winer EP, Wulf GM, and Matulonis UA, Abstract CT008: Phase I study of the alpha specific PI3-Kinase inhibitor BYL719 and the poly (ADP-Ribose) polymerase (PARP) inhibitor olaparib in recurrent ovarian and breast cancer: Analysis of the dose escalation and ovarian cancer expansion cohort. Cancer Res 2017;77(13 Suppl):Abstract nr CT008., 2017
    1. Moore KN, Martin LP, O’Malley DM, Matulonis UA, Konner JA, Perez RP, Bauer TM, Ruiz-Soto R, and Birrer MJ, Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study. J Clin Oncol, 2017. 35(10): p. 1112–1118.PMC5559878,http://www.ncbi.nlm.nih.gov/pubmed/28029313 - PMC - PubMed
    1. Brill E, Yokoyama T, Nair J, Yu M, Ahn YR, and Lee JM, Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer. Oncotarget, 2017. 8(67): p. 111026–111040.PMC5762302,http://www.ncbi.nlm.nih.gov/pubmed/29340034 - PMC - PubMed

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