TY - JOUR
T1 - VEGF-A expression correlates with TP53 mutations in non-small cell lung cancer
T2 - Implications for antiangiogenesis therapy
AU - Schwaederlé, Maria
AU - Lazar, Vladimir
AU - Validire, Pierre
AU - Hansson, Johan
AU - Lacroix, Ludovic
AU - Soria, Jean Charles
AU - Pawitan, Yudi
AU - Kurzrock, Razelle
N1 - Publisher Copyright:
©2015 AACR.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Bevacizumab is one of the most widely used antiangiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the tumor suppressor gene TP53, which occur frequently in many human malignancies. In this study, we present a multiple regression analysis of transcriptomic data in 123 patients with non-small cell lung cancer (NSCLC) showing that TP53 mutations are associated with higher VEGF-A expression (P = 0.006). This association was interesting given a recent retrospective study showing longer progression-free survival in patients with diverse tumors who receive bevacizumab, if tumors harbor mutant TP53 instead of wild-type TP53. Thus, our current findings linking TP53 mutation with VEGF-A upregulation offered a mechanistic explanation for why patients exhibit improved outcomes after bevacizumab treatment when their tumors harbor mutant TP53 versus wild-type TP53. Overall, this work warrants further evaluation of TP53 as a ready biomarker to predict bevacizumab response in NSCLC and possibly other tumor types.
AB - Bevacizumab is one of the most widely used antiangiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the tumor suppressor gene TP53, which occur frequently in many human malignancies. In this study, we present a multiple regression analysis of transcriptomic data in 123 patients with non-small cell lung cancer (NSCLC) showing that TP53 mutations are associated with higher VEGF-A expression (P = 0.006). This association was interesting given a recent retrospective study showing longer progression-free survival in patients with diverse tumors who receive bevacizumab, if tumors harbor mutant TP53 instead of wild-type TP53. Thus, our current findings linking TP53 mutation with VEGF-A upregulation offered a mechanistic explanation for why patients exhibit improved outcomes after bevacizumab treatment when their tumors harbor mutant TP53 versus wild-type TP53. Overall, this work warrants further evaluation of TP53 as a ready biomarker to predict bevacizumab response in NSCLC and possibly other tumor types.
UR - http://www.scopus.com/inward/record.url?scp=84929334169&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-14-2305
DO - 10.1158/0008-5472.CAN-14-2305
M3 - Article
C2 - 25672981
AN - SCOPUS:84929334169
SN - 0008-5472
VL - 75
SP - 1187
EP - 1190
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -