TY - JOUR
T1 - Targeting the folate receptor
T2 - Diagnostic and therapeutic approaches to personalize cancer treatments
AU - Ledermann, J. A.
AU - Canevari, Silvana
AU - Thigpen, T.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Background: In cancer therapy, molecularly targeted agents have the potential to maximize antitumor efficacy while minimizing treatment-related toxicity. However, these agents may only be effective in specific tumor subtypes with defined genomic profiles. This emphasizes the importance of developing personalized cancer therapeutic strategies (i.e. through the use of companion diagnostic tests) to appropriately select and treat patients who are likely to benefit from specific targeted therapies, thus leading to improvements in clinical and safety outcomes. A potential biological target is the folate receptor (FR), which has been shown to be overexpressed on the surface of many cancers, including tumors of the lungs and ovaries. Design: We carried out a literature search to identify how the FR can be a potential target for selected tumors, and how the FR expression can be exploited by targeted therapies. Results: The two main therapeutic strategies for targeting the FR are based on the use of: (i) an anti-FR antibody (e.g. farletuzumab) and (ii) folate conjugates of folate-targeted chemotherapies and companion radiodiagnostic imaging agents (e.g. vintafolide and 99mtechnetium-etarfolatide). Both of these strategies are being assessed in phase III trials. Conclusions: The important role that the FR plays in cancer development and progression has led to the development of FR-targeted therapeutic approaches. To date, the promising data observed in phase II clinical trials have not been confirmed in phase III studies. Accordingly, there is a need for further research in the refinement of patient selection and identification of new therapeutic combinations. In particular, the development of these targeted therapies requires reliable methods to be developed to detect FR-positive tumors in order to help select patients who may benefit from treatment.
AB - Background: In cancer therapy, molecularly targeted agents have the potential to maximize antitumor efficacy while minimizing treatment-related toxicity. However, these agents may only be effective in specific tumor subtypes with defined genomic profiles. This emphasizes the importance of developing personalized cancer therapeutic strategies (i.e. through the use of companion diagnostic tests) to appropriately select and treat patients who are likely to benefit from specific targeted therapies, thus leading to improvements in clinical and safety outcomes. A potential biological target is the folate receptor (FR), which has been shown to be overexpressed on the surface of many cancers, including tumors of the lungs and ovaries. Design: We carried out a literature search to identify how the FR can be a potential target for selected tumors, and how the FR expression can be exploited by targeted therapies. Results: The two main therapeutic strategies for targeting the FR are based on the use of: (i) an anti-FR antibody (e.g. farletuzumab) and (ii) folate conjugates of folate-targeted chemotherapies and companion radiodiagnostic imaging agents (e.g. vintafolide and 99mtechnetium-etarfolatide). Both of these strategies are being assessed in phase III trials. Conclusions: The important role that the FR plays in cancer development and progression has led to the development of FR-targeted therapeutic approaches. To date, the promising data observed in phase II clinical trials have not been confirmed in phase III studies. Accordingly, there is a need for further research in the refinement of patient selection and identification of new therapeutic combinations. In particular, the development of these targeted therapies requires reliable methods to be developed to detect FR-positive tumors in order to help select patients who may benefit from treatment.
KW - Etarfolatide
KW - Folate receptor
KW - Nonsmall-cell lung cancer
KW - Ovarian cancer
KW - Vintafolide
UR - http://www.scopus.com/inward/record.url?scp=84943764538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943764538&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdv250
DO - 10.1093/annonc/mdv250
M3 - Article
C2 - 26063635
AN - SCOPUS:84943764538
VL - 26
SP - 2034
EP - 2043
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 10
M1 - mdv250
ER -