Linifanib: current status and future potential in cancer therapy.
Angiogenesis is one of the major mechanisms controlling tumor proliferation and metastatic spreading. Targeting of pro-angiogenic factors and their downstream effectors represents an appealing therapeutic option in the treatment of different cancer types. Linifanib (ABT-869) is a novel tyrosine-kinase inhibitor (TKI) inhibitor and its anti-angiogenic activity has been explored in numerous clinical trials. Here, we review preclinical development of linifanib focusing on its pharmacodynamic and pharmacokinetic characteristics and briefly summarize its evaluation in clinical trials. Linifanib selectively targets VEGFR and PDGFR and has low off-target inhibitory activity. Preclinical and early-phase trials have been showing promising efficacy results However, although signals of anti-tumor activity have been proven in some malignancies, linifanib late-phase development has been facing some challenges due to limited efficacy and increased toxicities. New strategies aimed at finding biomarkers of response and minimizing toxicities are needed to allow the further development of a promising compound.
Department of Oncology, University of Torino Medical School, Torino, Italy.
Caterina
C
Aversa
Francesco
F
Leone
Giorgia
G
Zucchini
Guido
G
Serini
Elena
E
Geuna
Andrea
A
Milani
Donatella
D
Valdembri
Rossella
R
Martinello
Filippo
F
Montemurro
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007191:Indazoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C513486:linifanib
ABT-869; Linifanib; PDGF; VEGF; angiogenesis; chemotherapy