Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Jan 29:7:31-42.
doi: 10.2147/PGPM.S58374. eCollection 2014.

Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide

Loredana Serpe  1 , Margherita Gallicchio  1 , Roberto Canaparo  1 , Franco Dosio  1
Affiliations
Review

Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide

Loredana Serpe et al. Pharmgenomics Pers Med. .

Abstract

Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin) comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent "tumor-associated antigen". With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide) for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide) as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy.

Keywords: biomarkers; etarfolatide; folate receptor; platinum-resistant ovarian cancer; targeted therapy; vintafolide.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Mechanism of action of a folate-targeted drug conjugate.
Figure 2
Figure 2
Structure of folate-targeted therapeutic and diagnostic agents.
See this image and copyright information in PMC

References

    1. Siegel R, Naishadham D, Jemal A. Cancer Statistics, 2012. CA Cancer J Clin. 2012;62:10–29. - PubMed
    1. Whittemore AS. Characteristics relating to ovarian cancer risk: implications for prevention and detection. Gynecol Oncol. 1994;55(3 II):S15–S9. - PubMed
    1. Garg PP, Kerlikowske K, Subak L, Grady D. Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis. Obstet Gynecol. 1998;92(3):472–479. - PubMed
    1. Purdie D, Green A, Bain C, et al. Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case-control study. Int J Cancer. 1995;62(6):678–684. - PubMed
    1. Risch HA, Howe GR. Pelvic inflammatory disease and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 1995;4(5):447–451. - PubMed