Metastatic gynecologic malignancies: advances in treatment and management

Chan, John K.; Chow, Stephanie; Bhowmik, Subasish; Mann, Amandeep; Kapp, Daniel S.; Coleman, Robert L.

doi:10.1007/s10585-018-9889-7

Cited by 14 publications

(13 citation statements)

References 93 publications

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“…Ovarian cancer is a commonly diagnosed cancer worldwide and causes more deaths than any other cancer of the female reproductive system. It ranks among the top five deadliest cancers in most countries ( 48 ) and in the United States alone, each year about 20,000 women are diagnosed with ovarian cancer ( 60 ). KISS1 expression levels have also been linked to survival in ovarian cancer patients as reported in several studies.…”

Section: Metastasis Suppressor Rolesmentioning

confidence: 99%

KISS1/KISS1R in Cancer: Friend or Foe?

Guzman

Brackstone

Radovick³

et al. 2018

Front. Endocrinol.

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The KISS1 gene encodes KISS1, a protein that is rapidly processed in serum into smaller but biologically active peptides called kisspeptins (KPs). KISS1 and the KPs signal via the G-protein coupled receptor KISS1R. While KISS1 and KPs are recognized as potent positive regulators of the reproductive neuroendocrine axis in mammals, the first reported role for KISS1 was that of metastasis suppression in melanoma. Since then, it has become apparent that KISS1, KPs, and KISS1R regulate the development and progression of several cancers but interestingly, while these molecules act as suppressors of tumorigenesis and metastasis in many cancers, in breast and liver cancer they function as promoters. Thus, they join a small but growing number of molecules that exhibit dual roles in cancer highlighting the importance of studying cancer in context. Given their roles, KISS1, KPs and KISS1R represent important molecules in the development of novel therapies and/or as prognostic markers in treating cancer. However, getting to that point requires a detailed understanding of the relationship between these molecules and different cancers. The purpose of this review is therefore to highlight and discuss the clinical studies that have begun describing this relationship in varying cancer types including breast, liver, pancreatic, colorectal, bladder, and ovarian. An emerging theme from the reviewed studies is that the relationship between these molecules and a given cancer is complex and affected by many factors such as the micro-environment and steroid receptor status of the cancer cell. Our review and discussion of these important clinical studies should serve as a valuable resource in the successful development of future clinical studies.

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Section: Metastasis Suppressor Rolesmentioning

confidence: 99%

KISS1/KISS1R in Cancer: Friend or Foe?

Guzman

Brackstone

Radovick³

et al. 2018

Front. Endocrinol.

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“…The mainstays of ovarian cancer treatment include a defined combination of surgery and chemotherapy. Front line systemic chemotherapy includes platinum compounds and taxanes, with doxorubicin, topotecan, and gemcitabine as options in recurrent disease [9]. Additional therapies including anti-angiogenics and poly (ADP ribose) polymerase (PARP) inhibitors have been added to treatment regimens with the goal of extending the disease-free interval [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…Immune therapies targeting checkpoint blockades yield mixed results in clinical trials and toxicity is a concern [10]. There are ongoing efforts to identify new actionable targets in ovarian cancer and expand the therapeutic repertoire for this disease [3,4,5,7,8,9,12].…”

Section: Introductionmentioning

confidence: 99%

Dual Actions of Ketorolac in Metastatic Ovarian Cancer

Hudson

Cook

Grimes

et al. 2019

Cancers

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Cytoreductive surgery and chemotherapy are cornerstones of ovarian cancer treatment, yet disease recurrence remains a significant clinical issue. Surgery can release cancer cells into the circulation, suppress anti-tumor immunity, and induce inflammatory responses that support the growth of residual disease. Intervention within the peri-operative window is an under-explored opportunity to mitigate these consequences of surgery and influence the course of metastatic disease to improve patient outcomes. One drug associated with improved survival in cancer patients is ketorolac. Ketorolac is a chiral molecule administered as a 1:1 racemic mixture of the S- and R-enantiomers. The S-enantiomer is considered the active component for its FDA indication in pain management with selective activity against cyclooxygenase (COX) enzymes. The R-enantiomer has a previously unrecognized activity as an inhibitor of Rac1 (Ras-related C3 botulinum toxin substrate) and Cdc42 (cell division control protein 42) GTPases. Therefore, ketorolac differs from other non-steroidal anti-inflammatory drugs (NSAIDs) by functioning as two distinct pharmacologic entities due to the independent actions of each enantiomer. In this review, we summarize evidence supporting the benefits of ketorolac administration for ovarian cancer patients. We also discuss how simultaneous inhibition of these two distinct classes of targets, COX enzymes and Rac1/Cdc42, by S-ketorolac and R-ketorolac respectively, could each contribute to anti-cancer activity.

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“…The clonogenic assay is widely used to determine cell reproductive death after treatment with ionizing radiation. In 2D models, SKG-II cells and C-4I cells were treated with exo-miR22 or exo-cont miR, and irradiated with various radiation doses (2,4,6 and 8 Gy). Compared to the treatment of exocont miR, the survival fraction of the exo-miR22-treated group was lower in both SKG-II cells and C4-I cells, indicating increased radiosensitivity after treatment of exo-miR22 ( Figure 4).…”

Section: Radiosensitivity Was Enhanced By Exosomal Mir-22 In Vitromentioning

confidence: 99%

“…Over the years, cervical cancer screening and early treatment have reduced the incidence and mortality of cervical cancer. 1,2 However, the prognosis of advanced cervical cancer remains poor. Because advanced cervical cancers receive radiotherapy or chemoradiotherapy, radiotherapy is a critical component of the standard treatment regimen.…”

Section: Introductionmentioning

confidence: 99%