title: Anti-angiogenic drugs and biomarkers in non-small-cell lung cancer: a 'hard days night'.
abstract: The discovery of specific molecular alterations (i.e. EGFR activating mutations, EML4/ALK translocation, ROS1 rearrangements) in a selected population of patients affected by non small cell lung cancer (NSCLC) translated into effective treatments for this small but well defined fraction of patients, driven by the use of predictive biomarkers of efficacy for targeted agents. Unfortunately, the same reliable predictive biomarkers are lacking for anti-angiogenic drugs. Angiogenesis plays a major role in the progression of NSCLC, however, anti-angiogenic agents provided a minimal, although significant, clinical benefit in unselected populations, burdened by a not negligible toxicities. In this context, no validated angiogenic factor or other molecular biomarker of angiogenesis can reliably predict clinical outcome, sensitivity, early response or resistance to any of the investigated anti-angiogenic therapies currently used. Moreover, the available clinical data are prevalently retrospective, underpowered, and, in many cases, contradictory, thus underscoring that the understanding of the complex architecture of angiogenic signaling is still incomplete. We here review the currently available studies on the effect of anti-angiogenic drugs in NSCLC, with a particular focus on bio-molecular factors that are regarded as potential predictors of treatment efficacy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pilotto
authors.forename: Maria
authors.initials: M
authors.lastname: Bonomi
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.forename: Ludovica
authors.initials: L
authors.lastname: Ciuffreda
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Medical Oncology dU, Policlinico 'G.B. Rossi', University of Verona, P.zza L.A. Scuro 1, 37134, Verona, Italy. emiliobria@yahoo.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor