Design of New FSHR-Specific Peptides for therapeutic and diagnostic applications
Contact person: Annarita Del Gatto, annarita.delgatto
cnr.it
Actors: Annarita Del Gatto, annarita.delgattocnr.it, Laura Zaccaro, lzaccarounina.it,
Research areas: Small molecules and peptides/modified peptides for diagnostic, therapeutic and biotechnological applications,
Keywords: Design, synthesis, selective peptides, FSHβ, FSHR, tumor diagnosis, anti tumor therapy, anti tumor drugs
Contact person: Annarita Del Gatto, annarita.delgatto
cnr.itActors: Annarita Del Gatto, annarita.delgatto
cnr.it, Laura Zaccaro, lzaccarounina.it, Description:
Follicle-stimulating hormone (FSH) and its receptor (FSHR) are involved in reproduction in mammals. FSHR is normally expressed by cells of the testis and the ovary, and absent in other normal tissues. Recently, FSHR expression has been reported in vascular endothelial cells from primary and metastatic tumors, independently from their phenotype or behavior. Therefore, FSHR may be considered a pan-target in solid cancers, providing an invaluable opportunity for therapeutic and diagnostic applications. Despite FSHR unique characteristics, FSHR-based cancer imaging and therapy are currently at a preliminary stage, as only a few FSHR-targeting molecules have been tested in the preclinic models. On this ground, our research is focused on developing a new class of FSHR specific pharmaceuticals designed starting from the crystal structure of FSH/FSHR complex. They are linear and cyclic peptides FSHβ-derived opportunely functionalized for different types of labelling, currently under structural characterization by physicochemical methodologies and, in collaboration with researchers from IC-CNR, ICMATE-CNR and IOV-IRCCS, under biological investigation in vitro and in vivo preclinical models.
Our study may represent in the future a breakthrough in the field of oncology, since targeting FSHR in tumor blood vessels would allow the availability of a unique “weapon” for the diagnosis and treatment of most, if not all, primary and metastatic solid tumors.
Follicle-stimulating hormone (FSH) and its receptor (FSHR) are involved in reproduction in mammals. FSHR is normally expressed by cells of the testis and the ovary, and absent in other normal tissues. Recently, FSHR expression has been reported in vascular endothelial cells from primary and metastatic tumors, independently from their phenotype or behavior. Therefore, FSHR may be considered a pan-target in solid cancers, providing an invaluable opportunity for therapeutic and diagnostic applications. Despite FSHR unique characteristics, FSHR-based cancer imaging and therapy are currently at a preliminary stage, as only a few FSHR-targeting molecules have been tested in the preclinic models. On this ground, our research is focused on developing a new class of FSHR specific pharmaceuticals designed starting from the crystal structure of FSH/FSHR complex. They are linear and cyclic peptides FSHβ-derived opportunely functionalized for different types of labelling, currently under structural characterization by physicochemical methodologies and, in collaboration with researchers from IC-CNR, ICMATE-CNR and IOV-IRCCS, under biological investigation in vitro and in vivo preclinical models.
Our study may represent in the future a breakthrough in the field of oncology, since targeting FSHR in tumor blood vessels would allow the availability of a unique “weapon” for the diagnosis and treatment of most, if not all, primary and metastatic solid tumors.
Selected papers:
- Jiang, X.
et al. Evidence for Follicle-stimulating Hormone Receptor as a Functional
Trimer. J Biol Chem 2014, 289, 14273. doi: 10.1074/jbc.M114.549592.
- Siraj, A.
et al. Expression of follicle-stimulating hormone receptor by the vascular
endothelium in tumor metastases. BMC Cancer 2013, 13, 246. doi:
10.1186/1471-2407-13-246.
- Ghinea, N.
et al. Vascular Endothelial FSH Receptor, a Target of Interest for Cancer
Therapy. Endocrinology 2018, 159, 3268. doi:10.1210/en.2018-00466
Design of New FSHR-Specific Peptides for therapeutic and diagnostic applications
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Design of New FSHR-Specific Peptides for therapeutic and diagnostic applications
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