all‐trans retinoic acid for treating germ cell tumors: In vitro activity and results of a phase II trial Journal Article

  

Authors:	Moasser, M. M.; Motzer, R. J.; Khoo, K. S.; Lyn, P.; Murphy, B. A.; Bosl, G. J.; Dmitrovsky, E.
Article Title:	all‐trans retinoic acid for treating germ cell tumors: In vitro activity and results of a phase II trial
Abstract:	Background. Germ cell tumors (GCTs) are characterized by a capacity to differentiate in vivo and in vitro. The authors' previous work highlighted the finding that retinoid‐mediated GCT differentiation in vitro correlates with expression of the retinoic acid receptor‐gamma. Methods. Six human GCT cell lines were studied to determine whether their growth and differentiation were linked to the retinoic acid response pathway. The maturation and growth inhibitory responses to all‐trans retinoic acid (RA) were studied as well as the expression of retinoic acid receptor‐gamma (RAR‐γ). The clinical anti‐tumor activity of RA was studied in a Phase II trial of RA in patients with chemotherapy‐refractory GCTs. Results. The RA response pathway was correlated with the control of growth and maturation in three of the six GCT cell lines studied. In one GCT cell line, RA induced RAR‐γ expression and terminal differentiation. In a second, there was high basal expression of RAR‐γ and poor basal proliferative potential. A third cell line showed a more mature basal phenotype than other cell lines studied and marked growth inhibition when treated with RA. Sixteen patients were treated with RA for an average of 7 weeks in the clinical trial. No complete or partial responses were noted. Conclusion. A Phase II clinical trial of RA failed to show significant clinical antitumor activity in patients with chemotherapy‐refractory GCTs. However in vitro data suggest that the control of growth and maturation in some GCT cell lines involve the RA signaling pathway. Further studies are warranted to define the role that other retinoids with receptor selectivity or more favorable pharmacologic properties may play in the maturation or antitumor responses of GCTs. Cancer 1995;76 680–6. Copyright © 1995 American Cancer Society
Keywords:	adolescent; adult; human cell; clinical trial; cell proliferation; cell division; phase 2 clinical trial; gene expression; cell maturation; cell differentiation; antineoplastic activity; in vitro study; tumor cells, cultured; rna, messenger; cancer cell; neoplasms, germ cell and embryonal; germ cell tumor; germ cell tumors; rna, neoplasm; retinoic acid; differentiation; growth inhibition; middle age; growth inhibitors; tretinoin; receptors, retinoic acid; human; male; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; all‐trans retinoic acid; retinoic acid receptorγ
Journal Title:	Cancer
Volume:	76
Issue:	4
ISSN:	0008-543X
Publisher:	Wiley Blackwell
Date Published:	1995-08-15
Start Page:	680
End Page:	686
Language:	English
DOI:	10.1002/1097-0142(19950815)76:4<680::aid-cncr2820760423>3.0.co;2-9
PUBMED:	8625166
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028984044&doi=10.1002%2f1097-0142%2819950815%2976%3a4%3c680%3a%3aAID-CNCR2820760423%3e3.0.CO%3b2-9&partnerID=40&md5=a84a74301ca38a829ccea89e0cb23fe2
Notes:	Article -- Export Date: 28 August 2018 -- Source: Scopus

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