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Article

Anti-Angiogenic Treatment in Pseudomyxoma Peritonei—Still a Strong Preclinical Rationale

1
Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, P.O. Box 4953 Nydalen, 0424 Oslo, Norway
2
Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, P.O. Box 4953 Nydalen, 0424 Oslo, Norway
3
Department of Research, Innovation and Education, Norwegian Radium Hospital, Oslo University Hospital, P.O. Box 4953 Nydalen, 0424 Oslo, Norway
4
Institute of Clinical Medicine, University of Oslo, 0310 Oslo, Norway
5
Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, P.O. Box 4953 Nydalen, 0424 Oslo, Norway
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Marc Pocard and Olivier Glehen
Cancers 2021, 13(11), 2819; https://doi.org/10.3390/cancers13112819
Received: 11 May 2021 / Revised: 2 June 2021 / Accepted: 2 June 2021 / Published: 5 June 2021
Patients with pseudomyxoma peritonei that are not cured by the standard treatment (cytoreductive surgery and hyperthermic intraperitoneal chemotherapy) have no efficacious treatment options. Drugs that inhibit formation of new vessels (anti-angiogenic drugs) could be a therapeutic option for these patients. Using patient samples and animal models we show that angiogenesis is important in pseudomyxoma peritonei and that anti-angiogenic drugs may indeed have an effect. Our results support continued efforts to determine the role of anti-angiogenic treatment in pseudomyxoma peritonei.
Pseudomyxoma peritonei (PMP) is a rare, slow-growing cancer characterized by progressive accumulation of intraperitoneal mucinous tumor deposits. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) cures approximately 50% of patients, but in unresectable and recurrent cases, treatment options are limited. Anti-angiogenic treatment is being explored as a potential therapeutic option. Using PMP patient samples, microvessel densities (immunostaining for CD31 and CD105) and pro-angiogenic factors were analyzed, and the proliferative response upon incubation with human umbilical cord vascular endothelial cells (HUVEC) was determined. Growth inhibition by anti-angiogenic drugs was analyzed in patient-derived xenograft models of PMP. PMP tumor tissues were found to be highly vascularized and contained key pro-angiogenic factors, in particular related to vascular endothelial growth factor (VEGF) signaling, but interestingly, high levels of fibroblast growth factor 2 were also detected. HUVEC proliferation was stimulated upon incubation with fresh tumor samples and the observed proliferation could be inhibited by VEGF pathway inhibitor bevacizumab. In xenograft models the two VEGF pathway inhibitors, bevacizumab and aflibercept, inhibited tumor growth. This work reemphasizes the importance of angiogenesis as a major driver in PMP and strengthens the preclinical rationale for continued exploration of angiogenesis inhibition in the hope of providing novel treatment to a group of patients that have few other treatment options. View Full-Text
Keywords: pseudomyxoma peritonei; angiogenesis; in vivo; peritoneal metastases; peritoneal carcinomatosis pseudomyxoma peritonei; angiogenesis; in vivo; peritoneal metastases; peritoneal carcinomatosis
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MDPI and ACS Style

Andersson, Y.; Fleten, K.G.; Abrahamsen, T.W.; Reed, W.; Davidson, B.; Flatmark, K. Anti-Angiogenic Treatment in Pseudomyxoma Peritonei—Still a Strong Preclinical Rationale. Cancers 2021, 13, 2819. https://doi.org/10.3390/cancers13112819

AMA Style

Andersson Y, Fleten KG, Abrahamsen TW, Reed W, Davidson B, Flatmark K. Anti-Angiogenic Treatment in Pseudomyxoma Peritonei—Still a Strong Preclinical Rationale. Cancers. 2021; 13(11):2819. https://doi.org/10.3390/cancers13112819

Chicago/Turabian Style

Andersson, Yvonne, Karianne G. Fleten, Torveig W. Abrahamsen, Wenche Reed, Ben Davidson, and Kjersti Flatmark. 2021. "Anti-Angiogenic Treatment in Pseudomyxoma Peritonei—Still a Strong Preclinical Rationale" Cancers 13, no. 11: 2819. https://doi.org/10.3390/cancers13112819

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