Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

Bowtell, David D.L.; Böhm, Steffen; Ahmed, Ahmed A.; Aspuria, Paul Joseph; Bast, Robert C.; Beral, Valerie; Berek, Jonathan S.; Birrer, Michael J.; Blagden, Sarah P.; Bookman, Michael A.; Brenton, James D.; Chiappinelli, Katherine B.; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard J.; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G.; Iwanicki, Marcin P.; Karlan, Beth Y.; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A.; Lu, Karen H.; McNeish, Iain A.; Menon, Usha; Narod, Steven A.; Nelson, Brad H.; Nephew, Kenneth P.; Pharoah, Paul D.P.; Powell, Daniel J.; Ramos, Pilar; Romero, Iris L.; Scott, Clare L.; Sood, Anil K.; Stronach, Euan A.; Balkwill, Frances R.

doi:10.1038/nrc4019

Cited by 969 publications

(936 citation statements)

References 185 publications

(207 reference statements)

Supporting

Mentioning

892

Contrasting

Unclassified

Order By: Relevance

“…Clinical management of ovarian cancer remains a challenge, as patients often present with advanced metastatic disease at the time of diagnosis. Treatment for these patients is limited and entails surgical debulking followed by combination chemotherapy; however, tumor response rates remain poor (33). Coincidently, ovarian cancer represents an ideal setting to test the combination of AXL inhibitors and DNA-damaging agents, as patients are in critical need of new treatment options that can enhance the effects of standard-of-care chemotherapy.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

Kariolis¹,

Miao²,

Diep³

et al. 2016

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

Kariolis¹,

Miao²,

Diep³

et al. 2016

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…For the migration assay, SKOV-3 cells (5x10 3 /insert) in DMEM with 10% FBS (Hyclone; GE Healthcare Life Sciences) were seeded into a commercial Transwell insert (membrane pore size, 8 µm) and incubated with celastrol (0.125, 0.25 and 0.5 µM). After 24 h, cells that had migrated to the bottom of the filter were stained with crystal violet and counted under a light microscope.…”

Section: Methodsmentioning

confidence: 99%

“…The high mortality rate of this cancer is largely due to the fact that many patients present with advanced or metastatic disease (2). In addition, conventional treatment strategies such as chemotherapy and radiation are unlikely to reduce the metastatic frequency in ovarian cancer (3).…”

Section: Introductionmentioning

confidence: 99%

Celastrol inhibits migration and invasion through blocking the NF-κB pathway in ovarian cancer cells

Wang¹,

Zhai²,

Du³

2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Metastatic ovarian cancer is a major clinical challenge with poor prognosis and high mortality. Celastrol is a natural compound that has exhibits antiproliferative activity; however, its effects on metastasis-related phenotypes in ovarian cancer models are unclear. In the current study, the anti-invasive activities and associated signaling pathways of celastrol were determined in ovarian cancer cells. Cell proliferation was tested by MTT assay. Cell migration was detected by wound healing and Transwell assays, while cell invasion was detected by a Matrigel-coated Transwell method. In addition, nuclear factor (NF)-κB and matrix metalloproteinase (MMP) expression was examined by western blotting, and MMP-2/-9 activities were determined by gelatin zymography. At sub-toxic concentrations (<0.5 µM), celastrol inhibited migration and invasion in a concentration-dependent manner in SKOV-3 and OVCAR-3 cells. At the molecular level, celastrol blocked the canonical NF-κB pathway by inhibiting IκBα phosphorylation, and preventing IκBα degradation and p65 accumulation. Furthermore, the expression and activity of the NF-κB target protein MMP-9, but not MMP-2, were inhibited by celastrol. Furthermore, celastrol showed no synergistic effect with MG132, an NF-κB inhibitor. In conclusion, celastrol exhibited significant anti-invasive activities in ovarian cancer cells. Such functions may be mediated via NF-κB pathway blockade. The results of this in vitro study strengthen the value of applying celastrol as a potential clinical intervention modality for delaying ovarian cancer metastasis. This, celastrol warrants further preclinical investigation.

show abstract

“…gov). HGSOC is distinctive in that it shows an initial favourable response to platinum-based chemotherapy (1). This response is probably related to a high rate of defects in the homologous recombination (HR) DNA repair pathway, mainly due to mutations in BRCA1 and BRCA2.…”

Section: Introductionmentioning

confidence: 99%

Metronomic cyclophosphamide‑induced long‑term remission after recurrent high‑grade serous ovarian cancer: A case study

2017

View full text Add to dashboard Cite

Abstract. Metronomic oral cyclophosphamide has gained increasing interest in recent years as a promising maintenance therapy in advanced, platinum-sensitive, high-grade serous ovarian cancer (HGSOC). Metronomic treatment with cyclophosphamide refers to the frequent, usually daily, administration of a low (oral) dose of cyclophosphamide with no prolonged drug-free breaks. Main advantages of this treatment are the effective reduction of tumour activity, oral administration in an outpatient setting, low cost and the low toxicity profile. Metronomic oral cyclophosphamide can benefit patients suffering from types of cancer known to be sensitive to alkylating agents, such as platinum-sensitive HGSOC. In recent years, several publications have underlined the advantage of this regimen and possible explanations were explored. We here present a patient with multiple recurrences of metastasized HGSOC, platinum-sensitive, with an on-going complete response to monotherapy with oral cyclophosphamide. This observation supports that patients with relapsing HGSOC who responded to platinum-based chemotherapy and cannot continue platinum-based chemotherapy because of toxicity, can be offered a course of metronomic cyclophosphamide. This case may serve as a reminder that old drugs can be used successfully even in the age of new upcoming therapy such as anti-angiogenic agents (VEGF inhibitors) and poly-ADP-ribose polymerase (PARP) inhibitors.

show abstract

Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

Cited by 969 publications

References 185 publications

Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

Celastrol inhibits migration and invasion through blocking the NF-κB pathway in ovarian cancer cells

Metronomic cyclophosphamide‑induced long‑term remission after recurrent high‑grade serous ovarian cancer: A case study

Contact Info

Product

Resources

About