[Oral drugs inhibiting the VEGF pathway].
Angiogenesis does not initiate malignancy but promotes tumor progression and metastasis. Inhibiting angiogenesis is now a validated strategy for treatment of cancer. In order to do it, different ways are under investigation from cellular therapy to oral agents. Nowadays targeting angiogenesis with small molecules mainly concern inhibition of the VEGF receptors tyrosine kinase activity. Five molecules are currently in phase III trials and two of them (sunitinib and sorafenib) have been approved by the FDA for the treatment of advanced renal cancer. Despite those encouraging results, numerous points remain unclear. The toxicity profile seems to be favourable but long term effects could be problematic. Indeed, clinical trials have pointed out the role of VEGF pathway in the maintenance of numerous physiological functions. Moreover, none of the agents are specifically anti-angiogenic and the respective parts of the "off target" effects are difficult to evaluate. Simple and reliable surrogate markers of toxicity and efficacy are still lacking.
Ropert
Stanislas
S
Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris.
Mir
Olivier
O
Armand
Jean-Pierre
JP
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D001247:Asthenia / Q000139:chemically induced; D000077784:Axitinib; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010793:Phthalazines / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D011507:Proteinuria / Q000139:chemically induced; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D000077157:Sorafenib; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology
D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D010793:Phthalazines; D010880:Piperidines; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; C404768:vatalanib; D000077157:Sorafenib; D000077784:Axitinib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib; C452423:vandetanib