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Novel therapeutics in low-grade serous ovarian cancer
  1. Lauren Cobb and
  2. David Gershenson
  1. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Lauren Cobb, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; lpcobb{at}mdanderson.org

Abstract

Low-grade serous ovarian cancer is a rare subtype of epithelial ovarian cancer clinically characterized by younger age at diagnosis, relative chemoresistance, and prolonged survival compared with its high-grade serous counterpart. It is molecularly characterized by estrogen and progesterone receptor positivity, aberrations in the MAPK (mitogen-activated protein kinase) pathway, and wild-type TP53 expression pattern. As research into low-grade serous ovarian cancer as a distinct entity has been able to accelerate independently, we have learned more about its unique pathogenesis, oncogenic drivers, and opportunities for novel therapeutics. In the primary setting, cytoreductive surgery in combination with platinum-based chemotherapy remain the standard of care. However, low-grade serous ovarian cancer has demonstrated relative chemoresistance in the primary and recurrent settings. Endocrine therapy is also commonly utilized in the maintenance and recurrent settings and is being evaluated in the adjuvant setting. Given the many similarities of low-grade serous ovarian cancer to luminal breast cancer, many recent studies have utilized similar therapeutic strategies including endocrine therapy combinations with CDK (cyclin-dependent kinase) 4/6 inhibitors. Additionally, recent trials have investigated combination therapies targeting the MAPK pathway, including MEK (mitogen-activated protein kinase kinase), BRAF (v-raf murine sarcoma viral oncogene homolog B1), FAK (focal adhesion kinase), and PI3K (phosphatidylinositol 3-kinase) inhibition. In this review, we will outline these novel therapeutic strategies for low-grade serous ovarian cancer.

  • Ovarian Cancer
  • Gynecology
  • Cystadenocarcinoma, Serous

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Footnotes

  • Contributors In this review article, Drs LC and DG both contributed to the conceptualization, writing, and final approval of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests DG reports payments made to his institution from the National Cancer Institute (NRG Oncology), Novartis, and the GOG Foundation for research outside the submitted work; royalties from Elsevier and UpToDate outside the submitted work; consulting fees from Genentech, Onconova, Springworks, and Verastem outside the submitted work; and stock from Johnson & Johnson, Bristol Myers Squibb, and Procter and Gamble outside the submitted work. LC has nothing to report.

  • Provenance and peer review Commissioned; internally peer reviewed.