Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 10, Issue -, Pages 2547-2560Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S105896
Keywords
fibroblast growth factor 1; FGF receptor; targeted cancer therapy; cytotoxic conjugates; FGFR-dependent cancer; MMAE; auristatin
Categories
Funding
- National Science Centre, Poland [2011/02/A/NZ1/00066]
Ask authors/readers for more resources
Fibroblast growth factor receptors (FGFRs) are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1(V)), was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE), and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody-drug conjugates. The FGF1(V)-valine-citrulline-MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE) upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1(V)-vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available